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Biomarkers in Diagnosis and Prediction of Hepatocellular Carcinoma Recurrence (Review)

Biomarkers in Diagnosis and Prediction of Hepatocellular Carcinoma Recurrence (Review)

Malov S.I., Malov I.V., Dvornichenko V.V., Marche P.N., Decaens T., Macek-Jilkova Z., Yushchuk N.D.
Key words: hepatocellular carcinoma; screening; biomarkers; proteomics.
2019, volume 11, issue 2, page 183.
DOI: https://doi.org/10.17691/stm2019.11.2.23

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Hepatocellular carcinoma (HCC) is the second leading cause of death in oncological patients. The prognosis of the disease outcome depends directly on its timely detection. Currently, in the majority of countries, the diagnostic algorithm at the preclinical stage of tumor development includes determination of alpha-fetoprotein in combination with instrumental imaging techniques. This approach allows the detection of about 65–80% of liver tumors at an early stage (A according to the BCLC classification), whereas at a very early stage (0 according to the BCLC classification) only 32–50% of cases, the result which cannot be considered satisfactory. In this regard, the search for effective biomarkers of hepatocellular carcinoma is an important challenge that faces the world healthcare.

Advances in proteomics and genomics have led to the discovery of numerous promising markers which are now being clinically tested. Molecules of protein nature proposed as hepatocellular carcinoma tumor markers in different periods of time are described in this review. Comparative data on their effectiveness and specificity are also presented. The possibility of isolated or combined use of these biomarkers for risk assessment and early diagnosis of primary liver cancer is considered.

  1. Siegel R., Naishadham D., Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63(1): 11–30, https://doi.org/10.3322/caac.21166.
  2. Forner A., Llovet J.M., Bruix J. Hepatocellular carcinoma. Lancet 2012; 379(9822): 1245–1255, https://doi.org/10.1016/s0140-6736(11)61347-0.
  3. Scaggiante B., Kazemi M., Pozzato G., Dapas B., Farra R., Grassi M., Zanconati F., Grassi G. Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials. World J Gastroenterol 2014; 20(5): 1268–1288, https://doi.org/10.3748/wjg.v20.i5.1268.
  4. Bertuccio P., Turati F., Carioli G., Rodriguez T., La Vecchia C., Malvezzi M., Negri E. Global trends and predictions in hepatocellular carcinoma mortality. J Hepatol 2017; 67(2): 302–309, https://doi.org/10.1016/j.jhep.2017.03.011.
  5. Tsuchiya N., Sawada Y., Endo I., Saito K., Uemura Y., Nakatsura T. Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol 2015; 21(37): 10573, https://doi.org/10.3748/wjg.v21.i37.10573.
  6. Duarte-Salles T., Misra S., Stepien M., Plymoth A., Muller D., Overvad K., Olsen A., Tjønneland A., Baglietto L., Severi G., Boutron-Ruault M.C., Turzanski-Fortner R., Kaaks R., Boeing H., Aleksandrova K., Trichopoulou A., Lagiou P., Bamia C., Pala V., Palli D., Mattiello A., Tumino R., Naccarati A., Bueno-de-Mesquita H.B., Peeters P.H., Weiderpass E., Quirós J.R., Agudo A., Sánchez-Cantalejo E., Ardanaz E., Gavrila D., Dorronsoro M., Werner M., Hemmingsson O., Ohlsson B., Sjöberg K., Wareham N.J., Khaw K.T., Bradbury K.E., Gunter M.J., Cross A.J., Riboli E., Jenab M., Hainaut P., Beretta L. Circulating osteopontin and prediction of hepatocellular carcinoma development in a large European population. Cancer Prev Res (Phila) 2016; 9(9): 758–765, https://doi.org/10.1158/1940-6207.capr-15-0434.
  7. Bruix J., Gores G.J., Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut 2014; 63(5): 844–855, https://doi.org/10.1136/gutjnl-2013-306627.
  8. World Cancer Report 2014. Edited by Stewart B.W., Wild C. Lyon, France: International Agency for Research on Cancer; Geneva, Switzerland: WHO Press; 2014.
  9. Torre L.A., Bray F., Siegel R.L., Ferlay J., Lortet-Tieulent J., Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87–108, https://doi.org/10.3322/caac.21262.
  10. Rowe J., Ghouri Y., Mian I. Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis. J Carcinog 2017; 16(1): 1, https://doi.org/10.4103/jcar.jcar_9_16.
  11. Ozakyol A. Global epidemiology of hepatocellular carcinoma (HCC epidemiology). J Gastrointest Cancer 2017; 48(3): 238–240, https://doi.org/10.1007/s12029-017-9959-0.
  12. Breder V.V., Kosyrev V.Y., Kudashkin N.E., Laktionov K.K. Hepatocellular carcinoma as a social and medical problem in the Russian Federation. Medicinskij sovet 2016; 10: 10–18, https://doi.org/10.21518/2079-701x-2016-10-10-18.
  13. Chávez-López M.G., Zúñiga-García V., Pérez-Carreón J.I., Avalos-Fuentes A., Escobar Y., Camacho J. Eag1 channels as potential early-stage biomarkers of hepatocellular carcinoma. Biologics 2016; 10: 139–148, https://doi.org/10.2147/btt.s87402.
  14. Ette A.I., Ndububa D.A., Adekanle O., Ekrikpo U. Diagnostic utility of alpha-fetoprotein and des-gamma-carboxyprothrombin in nigerians with hepatocellular carcinoma. Niger J Clin Pract 2017; 20(10): 1267–1272, https://doi.org/10.4103/njcp.njcp_398_16.
  15. Kiriienko V.T., Zaitsev I.A., Hrushkevych V.V., Potii V.V. Screening and early diagnosis of hepatocellular carcinoma. Aktual’naa infektologia 2018; 6(2): 70–76, https://doi.org/10.22141/2312-413x.6.2.2018.131091.
  16. Durand F., Antoine C., Soubrane O. Liver transplantation in France. Liver Transpl 2019; 25(5): 763–770, https://doi.org/10.1002/lt.25419.
  17. Bertino G., Ardiri A., Malaguarnera M., Malaguarnera G., Bertino N., Calvagno G.S. Hepatocellualar carcinoma serum markers. Semin Oncol 2012; 39(4): 410–433, https://doi.org/10.1053/j.seminoncol.2012.05.001.
  18. Singal A.G., Pillai A., Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med 2014; 11(4): e1001624, https://doi.org/10.1371/journal.pmed.1001624.
  19. Reichl P., Mikulits W. Accuracy of novel diagnostic biomarkers for hepatocellular carcinoma: an update for clinicians (review). Oncol Rep 2016; 36(2): 613–625, https://doi.org/10.3892/or.2016.4842.
  20. Singal A.G., Mittal S., Yerokun O.A., Ahn C., Marrero J.A., Yopp A.C., Parikh N.D., Scaglione S.J. Hepatocellular carcinoma screening associated with early tumor detection and improved survival among patients with cirrhosis in the US. Am J Med 2017; 130(9): 1099–1106, https://doi.org/10.1016/j.amjmed.2017.01.021.
  21. White D.L., Thrift A.P., Kanwal F., Davila J., El-Serag H.B. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology 2017; 152(4): 812–820, https://doi.org/10.1053/j.gastro.2016.11.020.
  22. Montalbano M., Rastellini C., McGuire J.T., Prajapati J., Shirafkan A., Vento R., Cicalese L. Role of glypican-3 in the growth, migration and invasion of primary hepatocytes isolated from patients with hepatocellular carcinoma. Cell Oncol (Dordr) 2018; 41(2): 169–184, https://doi.org/10.1007/s13402-017-0364-2.
  23. Abdel-Rahman O., Cheung W.Y. Population-based assessment of the national comprehensive cancer network recommendations for baseline imaging of hepatocellular carcinoma. Med Oncol 2019; 36(3): 26, https://doi.org/10.1007/s12032-019-1248-2.
  24. Farvardin S., Patel J., Khambaty M., Yerokun O.A., Mok H., Tiro J.A., Yopp A.C., Parikh N.D., Marrero J.A., Singal A.G. Patient-reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis. Hepatology 2017; 65(3): 875–884, https://doi.org/10.1002/hep.28770.
  25. Simmons O., Fetzer D., Yokoo T., Marrero J.A., Yopp A., Kono Y., Parikh N.D., Browning T., Singal A.G. Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis. Aliment Pharmacol Ther 2017; 45(1): 169–177, https://doi.org/10.1111/apt.13841.
  26. Aubé C., Oberti F., Lonjon J., Pageaux G., Seror O., N’Kontchou G., Rode A., Radenne S., Cassinotto C., Vergniol J., Bricault I., Leroy V., Ronot M., Castera L., Michalak S., Esvan M., Vilgrain V.; CHIC Group. EASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice. Liver Int 2017; 37(10): 1515–1525, https://doi.org/10.1111/liv.13429.
  27. Ronot M., Fouque O., Esvan M., Lebigot J., Aubé C., Vilgrain V. Comparison of the accuracy of AASLD and LI-RADS criteria for the non-invasive diagnosis of HCC smaller than 3 cm. J Hepatol 2018; 68(4): 715–723, https://doi.org/10.1016/j.jhep.2017.12.014.
  28. Masuzaki R., Karp S.J., Omata M. New serum markers of hepatocellular carcinoma. Semin Oncol 2012; 39(4): 434–439, https://doi.org/10.1053/j.seminoncol.2012.05.009.
  29. Sengupta S., Parikh N.D. Biomarker development for hepatocellular carcinoma early detection: current and future perspectives. Hepat Oncol 2017; 4(4): 111–122, https://doi.org/10.2217/hep-2017-0019.
  30. She S., Xiang Y., Yang M., Ding X., Liu X., Ma L., Liu Q., Liu B., Lu Z., Li S., Liu Y., Ran X., Xu X., Hu H., Hu P., Zhang D., Ren H., Yang Y. C-reactive protein is a biomarker of AFP-negative HBV-related hepatocellular carcinoma. Int J Oncol 2015; 47(2): 543–554, https://doi.org/10.3892/ijo.2015.3042.
  31. Waidely E., Al-Yuobi A.R., Bashammakh A.S., El-Shahawi M.S., Leblanc R.M. Serum protein biomarkers relevant to hepatocellular carcinoma and their detection. Analyst 2016; 141(1): 36–44, https://doi.org/10.1039/c5an01884f.
  32. Sia D., Llovet J.M. Liver cancer: translating ‘-omics’ results into precision medicine for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2017; 14(10): 571–572, https://doi.org/10.1038/nrgastro.2017.103.
  33. Zhao S., Su G., Yang W., Yue P., Bai B., Lin Y., Zhang J., Ba Y., Luo Z., Liu X., Zhao L., Xie Y., Xu Y., Li S., Meng W., Xie X., Li X. Identification and comparison of differentiation-related proteins in hepatocellular carcinoma tissues by proteomics. Technol Cancer Res Treat 2017; 16(6): 1092–1101, https://doi.org/10.1177/1533034617732426.
  34. Torres-Mena J.E., Salazar-Villegas K.N., Sánchez-Rodríguez R., López-Gabiño B., Del Pozo-Yauner L., Arellanes-Robledo J., Villa-Treviño S., Gutiérrez-Nava M.A., Pérez-Carreón J.I. Aldo-keto reductases as early biomarkers of hepatocellular carcinoma: a comparison between animal models and human HCC. Dig Dis Sci 2018; 63(4): 934–944, https://doi.org/10.1007/s10620-018-4943-5.
  35. Calvaruso V., Cabibbo G., Cacciola I., Petta S., Madonia S., Bellia A., Tinè F., Distefano M., Licata A., Giannitrapani L., Prestileo T., Mazzola G., Di Rosolini M.A., Larocca L., Bertino G., Digiacomo A., Benanti F., Guarneri L., Averna A., Iacobello C., Magro A., Scalisi I., Cartabellotta F., Savalli F., Barbara M., Davì A., Russello M., Scifo G., Squadrito G., Cammà C., Raimondo G., Craxì A., Di Marco V.; Rete Sicilia Selezione Terapia–HCV (RESIST-HCV). Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroenterology 2018; 155(2): 411–421, https://doi.org/10.1053/j.gastro.2018.04.008.
  36. Tatarinov Iu.S. Detection of embryo-specific alpha-globulin in the blood serum of a patient with primary liver cancer. Voprosy meditsinskoi khimii 1964; 10: 90–91.
  37. Abelev G.I. Production of embrional serum alpha-globulin by hepatomas: review of experimental and clinical data. Cancer Res 1968; 28(7): 1344–1350.
  38. Rich N., Singal A.G. Hepatocellular carcinoma tumour markers: current role and expectations. Best Pract Res Clin Gastroenterol 2014; 28(5): 843–853, https://doi.org/10.1016/j.bpg.2014.07.018.
  39. Bai D.S., Zhang C., Chen P., Jin S.J., Jiang G.Q. The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma. Sci Rep 2017; 7(1): 12870, https://doi.org/10.1038/s41598-017-12834-1.
  40. Gao J., Song P. Combination of triple biomarkers AFP, AFP-L3, and PIVAKII for early detection of hepatocellular carcinoma in China: expectation. Drug Discov Ther 2017; 11(3): 168–169, https://doi.org/10.5582/ddt.2017.01036.
  41. Li J., Chen X., Dai M., Huang S., Chen J., Dai S. Diagnostic accuracy of osteopontin plus alpha-fetoprotein in the hepatocellular carcinoma: a meta-analysis. Clin Res Hepatol Gastroenterol 2017; 41(5): 543–553, https://doi.org/10.1016/j.clinre.2017.01.010.
  42. Shen Q., Eun J.W., Lee K., Kim H.S., Yang H.D., Kim S.Y., Lee E.K., Kim T., Kang K., Kim S., Min D.H., Oh S.N., Lee Y.J., Moon H., Ro S.W., Park W.S., Lee J.Y., Nam S.W. Barrier to autointegration factor 1, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, and splicing factor 3b subunit 4 as early-stage cancer decision markers and drivers of hepatocellular carcinoma. Hepatology 2018; 67(4): 1360–1377, https://doi.org/10.1002/hep.29606.
  43. Liebman H.A., Furie B.C., Tong M.J., Blanchard R.A., Lo K.J., Lee S.D., Coleman M.S., Furie B. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 1984; 310: 1427–1431, https://doi.org/10.1056/nejm198405313102204.
  44. Poté N., Cauchy F., Albuquerque M., Voitot H., Belghiti J., Castera L., Puy H., Bedossa P., Paradis V. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J Hepatol 2015; 62(4): 848–854, https://doi.org/10.1016/j.jhep.2014.11.005.
  45. Haque S., Kumari R., Muzaffar A., Kumar U., Sharan A., Kumari B. Estimation of serum alpha feto-protein (AFP), interlukin-6 and des-γ-carboxyprothrombin (DCP) in case of hepatocellular carcinoma. Bangladesh Journal of Medical Science 2016; 15(2): 230–233, https://doi.org/10.3329/bjms.v15i2.19602.
  46. Jang E.S., Jeong S.-H., Kim J.-W., Choi Y.S., Leissner P., Brechot C. Diagnostic performance of alpha-fetoprotein, protein induced by vitamin K absence, osteopontin, dickkopf-1 and its combinations for hepatocellular carcinoma. PLoS One 2016; 11(3): e0151069, https://doi.org/10.1371/journal.pone.0151069.
  47. Chen J., Wu G., Li Y. Evaluation of serum des-gamma-carboxy prothrombin for the diagnosis of hepatitis virus-related hepatocellular carcinoma: a meta-analysis. Dis Markers 2018 4; 2018; 8906023, https://doi.org/10.1155/2018/8906023.
  48. Svobodova S., Karlikova M., Topolcan O., Pecen L., Pestova M., Kott O., Treska V., Slouka D., Kucera R. PIVKA-II as a potential new biomarker for hepatocellular carcinoma — a pilot study. In Vivo 2018; 32(6): 1551–1554, https://doi.org/10.21873/invivo.11413.
  49. Taketa K., Sekiya C., Namiki M., Akamatsu K., Ohta Y., Endo Y., Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology 1990; 99(2): 508–518, https://doi.org/10.1016/0016-5085(90)91034-4.
  50. Taketa K., Endo Y., Sekiya C., Tanikawa K., Koji T., Taga H., Satomura S., Matsuura S., Kawai T., Hirai H. A collaborative study for the evaluation of lectin-reactive α-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res 1993; 53(22): 5419–5423.
  51. Marrero J.A., Feng Z., Wang Y., Nguyen M.H., Befeler A.S., Roberts L.R., Reddy K.R., Harnois D., Llovet J.M., Normolle D., Dalhgren J., Chia D., Lok A.S., Wagner P.D., Srivastava S., Schwartz M. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009; 137(1): 110–118, https://doi.org/10.1053/j.gastro.2009.04.005.
  52. Park S.J., Jang J.Y., Jeong S.W., Cho Y.K., Lee S.H., Kim S.G., Cha S.W., Kim Y.S., Cho Y.D., Kim H.S., Kim B.S., Park S., Bang H.I. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma. Medicine (Baltimore) 2017; 96(11): e5811, https://doi.org/10.1097/md.0000000000005811.
  53. Giardina M., Matarazzo M., Varriale A., Morante R., Napoli A., Martino R. Serum alpha-L-fucosidase. A useful marker in the diagnosis of hepatocellular carcinoma. Cancer 1992; 70(5): 1044–1048, https://doi.org/10.1002/1097-0142(19920901) 70:51044::aid-cncr28207005063.0.co;2-u.
  54. Sergeev M.N., Shevaldin A.G., Rakhmanova A.G., Sleptsova S.S., Lyashenko E.A., Sharoyko V.V. Molecular markers of hepatocellular carcinoma. perspectives of early diagnostics. VICh-infektsiya i immunosupressii 2014; 6(3): 16–23.
  55. Trevisani F., D’Intino P.E., Morselli-Labate A.M., Mazzella G., Accogli E., Caraceni P., Domenicali M., De Notariis S., Roda E., Bernardi M. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol 2001; 34(4): 570–575, https://doi.org/10.1016/s0168-8278(00)00053-2.
  56. Junna Z., Gongde C., Jinying X., Xiu Z. Serum AFU, 5’-NT and AFP as biomarkers for primary hepatocellular carcinoma diagnosis. Open Med (Wars) 2017; 12(1): 354–358, https://doi.org/10.1515/med-2017-0051.
  57. Hsu H.C., Cheng W., Lai P.L. Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution. Cancer Res 1997; 57(22): 5179–5184.
  58. Capurro M., Wanless I.R., Sherman M., Deboer G., Shi W., Miyoshi E., Filmus J. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 2003; 125(1): 89–97, https://doi.org/10.1016/s0016-5085(03)00689-9.
  59. Qiao S.S., Cui Z.Q., Gong L., Han H., Chen P.C., Guo L.M., Yu X., Wei Y.H., Ha S.A., Kim J.W., Jin Z.T., Li S., Peng J.R., Leng X.S. Simultaneous measurements of serum AFP, GPC-3 and HCCR for diagnosing hepatocellular carcinoma. Hepatogastroenterology 2011; 58(110–111): 1718–1724, https://doi.org/10.5754/hge11124.
  60. Tangkijvanich P., Chanmee T., Komtong S., Mahachai V., Wisedopas N., Pothacharoen P., Kongtawelert P. Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers. J Gastroenterol Hepatol 2010; 25(1): 129–137, https://doi.org/10.1111/j.1440-1746.2009.05988.x.
  61. Jia X., Liu J., Gao Y., Huang Y., Du Z. Diagnosis accuracy of serum glypican-3 in patients with hepatocellular carcinoma: a systematic review with meta-analysis. Arch Med Res 2014; 45(7): 580–588, https://doi.org/10.1016/j.arcmed.2014.11.002.
  62. Haruyama Y., Kataoka H. Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma. World J Gastroenterol 2016; 22(1): 275–283, https://doi.org/10.3748/wjg.v22.i1.275.
  63. Montalbano M., Georgiadis J., Masterson A.L., McGuire J.T., Prajapati J., Shirafkan A., Rastellini C., Cicalese L. Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma (review). Oncol Rep 2017; 37(3): 1291–1300, https://doi.org/10.3892/or.2017.5387.
  64. Xu D., Su C., Sun L., Gao Y., Li Y. Performance of serum glypican 3 in diagnosis of hepatocellular carcinoma: a meta-analysis. Ann Hepatol 2018; 18(1): 58–67, https://doi.org/10.5604/01.3001.0012.7863.
  65. Marrero J.A., Romano P.R., Nikolaeva O., Steel L., Mehta A., Fimmel C.J., Comunale M.A., D’Amelio A., Lok A.S., Block T.M. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005; 43(6): 1007–1012, https://doi.org/10.1016/j.jhep.2005.05.028.
  66. Hu J.S., Wu D.W., Liang S., Miao X.Y. GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B-endemic Asian population. Med Oncol 2010; 27(2): 339–345, https://doi.org/10.1007/s12032-009-9215-y.
  67. Jiao C., Cui L., Piao J., Qi Y., Yu Z. Clinical significance and expression of serum Golgi protein 73 in primary hepatocellular carcinoma. J Cancer Res Ther 2018; 14(6): 1239–1244, https://doi.org/10.4103/0973-1482.199784.
  68. Giannelli G., Marinosci F., Trerotoli P., Volpe A., Quaranta M., Dentico P., Antonaci S. SCCA antigen combined with alpha-fetoprotein as serologic markers of HCC. Int J Cancer 2005; 117(3): 506–509, https://doi.org/10.1002/ijc.21189.
  69. Giannelli G., Fransvea E., Trerotoli P., Beaugrand M., Marinosci F., Lupo L., Nkontchou G., Dentico P., Antonaci S. Clinical validation of combined serological biomarkers for improved hepatocellular carcinoma diagnosis in 961 patients. Clin Chim Acta 2007; 383(1–2): 147–152, https://doi.org/10.1016/j.cca.2007.05.014.
  70. Witjes C.D., van Aalten S.M., Steyerberg E.W., Borsboom G.J., de Man R.A., Verhoef C., Ijzermans J.N. Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatol Int 2013; 7(1): 59–64, https://doi.org/10.1007/s12072-012-9374-3.
  71. Pozzan C., Cardin R., Piciocchi M., Cazzagon N., Maddalo G., Vanin V., Giacomin A., Pontisso P., Cillo U., Farinati F. Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC). J Gastroenterol Hepatol 2014; 29(8): 1637–1644, https://doi.org/10.1111/jgh.12576.
  72. Liu C.H., Gil-Gómez A., Ampuero J., Romero-Gómez M. Diagnostic accuracy of SCCA and SCCA-IgM for hepatocellular carcinoma: a meta-analysis. Liver Int 2018; 38(10): 1820–1831, https://doi.org/10.1111/liv.13867.
  73. Beneduce L., Castaldi F., Marino M., Quarta S., Ruvoletto M., Benvegnù L., Calabrese F., Gatta A., Pontisso P., Fassina G. Squamouse cell carcinoma antigen-immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma. Cancer 2005; 103(12): 2558–2565, https://doi.org/10.1002/cncr.21106.
  74. Kim J., Ki S.S., Lee S.D., Han C.J., Kim Y.C., Park S.H., Cho S.Y., Hong Y.J., Park H.Y., Lee M., Jung H.H., Lee K.H., Jeong S.H. Elevated plasma osteopontin levels in patients with hepatocellular carcinoma. Am J Gastroenterol 2006; 101(9): 2051–2059, https://doi.org/10.1111/j.1572-0241.2006.00679.x.
  75. Shang S., Plymoth A., Ge S., Feng Z., Rosen H.R., Sangrajrang S., Hainaut P., Marrero J.A., Beretta L. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2012; 55(2): 483–490, https://doi.org/10.1002/hep.24703.
  76. Wan H.G., Xu H., Gu Y.M., Wang H., Xu W., Zu M.H. Comparison osteopontin vs AFP for the diagnosis of HCC: a meta-analysis. Clin Res Hepatol Gastroenterol 2014; 38(6): 706–714, https://doi.org/10.1016/j.clinre.2014.06.008.
  77. Ge T., Shen Q., Wang N., Zhang Y., Ge Z., Chu W., Lv X., Zhao F., Zhao W., Fan J., Qin W. Diagnostic values of alpha-fetoprotein, dickkopf-1, and osteopontin for hepatocellular carcinoma. Med Oncol 2015; 32(3): 59, https://doi.org/10.1007/s12032-014-0367-z.
  78. Ji N.Y., Park M.Y., Kang Y.H., Lee C.I., Kim D.G., Yeom Y.I., Jang Y.J., Myung P.K., Kim J.W., Lee H.G., Kim J.W., Lee K., Song E.Y. Evaluation of annexin II as a potential serum marker for hepatocellular carcinoma using a developed sandwich ELISA method. Int J Mol Med 2009; 24(6): 765–771, https://doi.org/10.3892/ijmm_00000290.
  79. Sun Y., Gao G., Cai J., Wang Y., Qu X., He L., Liu F., Zhang Y., Lin K., Ma S., Yang X., Qian X., Zhao X. Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma. Carcinogenesis 2013; 34(3): 595–604, https://doi.org/10.1093/carcin/bgs372.
  80. Shaker M.K., Abdel Fattah H.I., Sabbour G.S., Montasser I.F., Abdelhakam S.M., El Hadidy E., Yousry R., El Dorry A.K. Annexin A2 as a biomarker for hepatocellular carcinoma in Egyptian patients. World J Hepatol 2017; 9(9): 469–476, https://doi.org/10.4254/wjh.v9.i9.469.
  81. Toyoda H., Kumada T., Tada T., Kaneoka Y., Maeda A., Kanke F., Satomura S. Clinical utility of highly sensitive lens culinaris agglutinin-reactive alpha-fetoprotein in hepatocellular carcinoma patients with alpha-fetoprotein <20 ng/ml. Cancer Sci 2011; 102(5): 1025–1031, https://doi.org/10.1111/j.1349-7006.2011.01875.x.
  82. Oda K., Ido A., Tamai T., Matsushita M., Kumagai K., Mawatari S., Saishoji A., Kure T., Ohno K., Toyokura E., Imanaka D., Moriuchi A., Uto H., Oketani M., Hashiguchi T., Tsubouchi H. Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease. Oncol Rep 2011; 26(5): 1227–1233, https://doi.org/10.3892/or.2011.1425.
  83. Tung E.K., Ng I.O. Significance of serum DKK1 as a diagnostic biomarker in hepatocellular carcinoma. Future Oncol 2012; 8(12): 1525–1528, https://doi.org/10.2217/fon.12.147.
  84. Shen Q., Fan J., Yang X.R., Tan Y., Zhao W., Xu Y., Wang N., Niu Y., Wu Z., Zhou J., Qiu S.J., Shi Y.H., Yu B., Tang N., Chu W., Wang M., Wu J., Zhang Z., Yang S., Gu J., Wang H., Qin W. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol 2012; 13(8): 817–826, https://doi.org/10.1016/s1470-2045(12)70233-4.
  85. Zhang J., Zhao Y., Yang Q. Sensitivity and specificity of dickkopf-1 protein in serum for diagnosing hepatocellular carcinoma: a meta-analysis. Int J Biol Markers 2014; 29(4): 403–410, https://doi.org/10.5301/jbm.5000101.
  86. Van Hees S., Michielsen P., Vanwolleghem T. Circulating predictive and diagnostic biomarkers for hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol 2016; 22(37): 8271–8282, https://doi.org/10.3748/wjg.v22.i37.8271.
  87. Qin Q.F., Weng J., Xu G.X., Chen C.M., Jia C.K. Combination of serum tumor markers dickkopf-1, DCP and AFP for the diagnosis of primary hepatocellular carcinoma. Asian Pac J Trop Med 2017; 10(4): 409–413, https://doi.org/10.1016/j.apjtm.2017.03.016.
  88. Reichl P., Fang M., Starlinger P., Staufer K., Nenutil R., Muller P., Greplova K., Valik D., Dooley S., Brostjan C., Gruenberger T., Shen J., Man K., Trauner M., Yu J., Gao C.F., Mikulits W. Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma. Int J Cancer 2015; 137(2): 385–394, https://doi.org/10.1002/ijc.29394.
  89. Dengler M., Staufer K., Huber H., Stauber R., Bantel H., Weiss K.H., Starlinger P., Pock H., Klöters-Plachky P., Gotthardt D.N., Rauch P., Lackner C., Stift J., Brostjan C., Gruenberger T., Kumada T., Toyoda H., Tada T., Weiss T.S., Trauner M., Mikulits W. Soluble Axl is an accurate biomarker of cirrhosis and hepatocellular carcinoma development: results from a large scale multicenter analysis. Oncotarget 2017; 8(28): 46234–46248, https://doi.org/10.18632/oncotarget.17598.
  90. Zhu W.-W., Guo J.-J., Guo L., Jia H.L., Zhu M., Zhang J.B., Loffredo C.A., Forgues M., Huang H., Xing X.J., Ren N., Dong Q.Z., Zhou H.J., Ren Z.G., Zhao N.Q., Wang X.W., Tang Z.Y., Qin L.X., Ye Q.H. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma. Clin Cancer Res 2013; 19(14): 3944–3954, https://doi.org/10.1158/1078-0432.ccr-12-3363.
  91. Shaheen K.Y., Abdel-Mageed A.I., Safwat E., AlBreedy A.M. The value of serum midkine level in diagnosis of hepatocellular carcinoma. Int J Hepatol 2015; 2015: 146389, https://doi.org/10.1155/2015/146389.
  92. Vongsuvanh R., van Der Poorten D., Iseli T., Strasser S.I., McCaughan G.W., George J. Midkine increases diagnostic yield in AFP negative and NASH-related hepatocellular carcinoma. PLoS One 2016; 11(5): e0155800, https://doi.org/10.1371/journal.pone.0155800.
  93. Zheng T., Chen M., Han S., Zhang L., Bai Y., Fang X., Ding S.Z., Yang Y. Plasma minichromosome maintenance complex component 6 is a novel biomarker for hepatocellular carcinoma patients. Hepatol Res 2014; 44(13): 1347–1356, https://doi.org/10.1111/hepr.12303.
  94. Li J., Cheng Z.J., Liu Y., Yan Z.L., Wang K., Wu D., Wan X.Y., Xia Y., Lau W.Y., Wu M.C., Shen F. Serum thioredoxin is a diagnostic marker for hepatocellular carcinoma. Oncotarget 2015; 6(11): 9551–9563, https://doi.org/10.18632/oncotarget.3314.
  95. Chounta A., Ellinas C., Tzanetakou V., Pliarhopoulou F., Mplani V., Oikonomou A., Leventogiannis K., Giamarellos-Bourboulis E.J. Serum soluble urokinase plasminogen activator receptor as a screening test for the early diagnosis of hepatocellular carcinoma. Liver Int 2015; 35(2): 601–607, https://doi.org/10.1111/liv.12705.
  96. Gupta S., Bent S., Kohlwes J. Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med 2003; 139(1): 46–50, https://doi.org/10.7326/0003-4819-139-1-200307010-00012.
  97. Yang J.D., Dai J., Singal A.G., Gopal P., Addissie B.D., Nguyen M.H., Befeler A.S., Reddy K.R., Schwartz M., Harnois D.M., Yamada H., Gores G.J., Feng Z., Marrero J.A., Roberts L.R. Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in HCV cirrhosis with normal alanine transaminase. Cancer Epidemiol Biomarkers Prev 2017; 26(7): 1085–1092, https://doi.org/10.1158/1055-9965.epi-16-0747.
  98. Sauzay C., Petit A., Bourgeois A.M., Barbare J.C., Chauffert B., Galmiche A., Houessinon A. Alpha-foetoprotein (AFP): a multi-purpose marker in hepatocellular carcinoma. Clin Chim Acta 2016; 463: 39–44, https://doi.org/10.1016/j.cca.2016.10.006.
  99. Yen C.W., Kuo Y.H., Wang J.H., Chang K.C., Kee K.M., Hung S.F., Chen Y., Tsai L.S., Chen S.C., Hung C.H., Lu S.N. Did AFP-L3 save ultrasonography in community screening? Kaohsiung J Med Sci 2018; 34(10): 583–587, https://doi.org/10.1016/j.kjms.2018.05.005.
  100. McMahon B.J., Bulkow L., Harpster A., Snowball M., Lanier A., Sacco F., Dunaway E., Williams J. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology 2000; 32(4 Pt 1): 842–846, https://doi.org/10.1053/jhep.2000.17914.
  101. Sterling R.K., Jeffers L., Gordon F., Venook A.P., Reddy K.R., Satomura S., Kanke F., Schwartz M.E., Sherman M. Utility of lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol 2009; 7(1): 104–113, https://doi.org/10.1016/j.cgh.2008.08.041.
  102. Unić A., Derek L., Duvnjak M., Patrlj L., Rakić M., Kujundžić M., Renjić V., Štoković N., Dinjar P., Jukic A., Grgurević I. Diagnostic specificity and sensitivity of PIVKAII, GP3, CSTB, SCCA1 and HGF for the diagnosis of hepatocellular carcinoma in patients with alcoholic liver cirrhosis. Ann Clin Biochem 2018; 55(3): 355–362, https://doi.org/10.1177/0004563217726808.
  103. Hemken P.M., Sokoll L.J., Yang X., Dai J., Elliott D., Gawel S.H., Lucht M., Feng Z., Marrero J.A., Srivastava S., Chan D.W., Davis G.J. Validation of a novel model for the early detection of hepatocellular carcinoma. Clin Proteomics 2019; 16: 2, https://doi.org/10.1186/s12014-018-9222-0.
  104. Yamashiki N., Sugawara Y., Tamura S., Kaneko J., Yoshida H., Aoki T., Hasegawa K., Akahane M., Ohtomo K., Fukayama M., Koike K., Kokudo N. Diagnostic accuracy of alpha-fetoprotein and des-gamma-carboxy prothrombin in screening for hepatocellular carcinoma in liver transplant candidates. Hepatol Res 2011; 41(12): 1199–1207, https://doi.org/10.1111/j.1872-034x.2011.00871.x.
  105. Best J., Bilgi H., Heider D., Schotten C., Manka P., Bedreli S., Gorray M., Ertle J., van Grunsven L.A., Dechene A. The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma. Z Gastroenterol 2016; 54(12): 1296–1305, https://doi.org/10.1055/s-0042-119529.
  106. Wu J., Xiang Z., Bai L., He L., Tan L., Hu M., Ren Y. Diagnostic value of serum PIVKA-II levels for BCLC early hepatocellular carcinoma and correlation with HBV DNA. Cancer Biomark 2018; 23(2): 235–242, https://doi.org/10.3233/cbm-181402.
  107. Yu R., Tan Z., Xiang X., Dan Y., Deng G. Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data. BMC Cancer 2017; 17(1): 608, https://doi.org/10.1186/s12885-017-3609-6.
  108. Shuang Z., Mao Y., Lin G., Wang J., Huang X., Chen J., Duan F., Li S. Alpha-L-fucosidase serves as a prognostic indicator for intrahepatic cholangiocarcinoma and inhibits its invasion capacity. Biomed Res Int 2018; 2018: 8182575, https://doi.org/10.1155/2018/8182575.
  109. López Vivancos J., Segura R.M., Oliva G., Vives L., Pascual C., Vilaseca J. Value of the serum measurement of alpha-L-fucosidase in the diagnosis of hepatocarcinoma. Med Clin (Barc) 1989; 93(7): 241–243.
  110. Ishizuka H., Nakayama T., Matsuoka S., Gotoh I., Ogawa M., Suzuki K., Tanaka N., Tsubaki K., Ohkubo H., Arakawa Y., Okano T. Prediction of the development of hepato-cellular-carcinoma in patients with liver cirrhosis by the serial determinations of serum alpha-L-fucosidase activity. Intern Med 1999; 38(12): 927–931, https://doi.org/10.2169/internalmedicine.38.927.
  111. Gotoh M., Nakatani T., Masuda T., Mizuguchi Y., Sakamoto M., Tsuchiya R., Kato H., Furuta K. Prediction of invasive activities in hepatocellular carcinomas with special reference to alpha-fetoprotein and des-gamma-carboxyprothrombin. Jpn J Clin Oncol 2003; 33(10): 522–526, https://doi.org/10.1093/jjco/hyg096.
  112. Attallah A.M., El-Far M., Omran M.M., Abdelrazek M.A., Attallah A.A., Saeed A.M., Farid K. GPC-HCC model: a combination of glybican-3 with other routine parameters improves the diagnostic efficacy in hepatocellular carcinoma. Tumor Biol 2016; 37(9): 12571–12577, https://doi.org/10.1007/s13277-016-5127-6.
  113. Majeed S., Mushtaq S., Azam M., Akhtar N., Hussain M., Loya A. Diagnostic accuracy of glypican-3 in differentiating hepatocellular carcinoma from metastatic liver tumours. J Pak Med Assoc 2018; 68(7): 1029–1031.
  114. Liang R., Liu Z., Piao X., Zuo M., Zhang J., Liu Z., Li Y., Lin Y. Research progress on GP73 in malignant tumors. Onco Targets Ther 2018; 11: 7417–7421, https://doi.org/10.2147/ott.s181239.
  115. Ismail M.M., Morsi H.K., Abdulateef N.A., Noaman M.K., Abou El-Ella G.A. Evaluation of prothrombin induced by vitamin K absence, macrophage migration inhibitory factor and Golgi protein-73 versus alpha fetoprotein for hepatocellular carcinoma diagnosis and surveillance. Scand J Clin Lab Invest 2017; 77(3): 175–183, https://doi.org/10.1080/00365513.2017.1286684.
  116. Farag R.M.A., Al Ayobi D., Alsaleh K.A., Kwon H.J., EL-Ansary A., Dawoud E.A. Studying the impact of Golgi protein 73 serving as a candidate biomarker in early diagnosis for hepatocellular carcinoma among Saudi patients. Asian Pac J Cancer Prev 2019; 20(1): 215–220, https://doi.org/10.31557/apjcp.2019.20.1.215.
  117. Xu W.J., Guo B.L., Han Y.G., Shi L., Ma W.S. Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumor Biol 2014; 35(12): 12069–12074, https://doi.org/10.1007/s13277-014-2506-8.
  118. Guarino M., Di Costanzo G.G., Gallotta A., Tortora R., Paneghetti L., Auriemma F., Tuccillo C., Fassina G., Caporaso N., Morisco F. Circulating SCCA-IgM complex is a useful biomarker to predict the outcome of therapy in hepatocellular carcinoma patients. Scand J Clin Lab Invest 2017; 77(6): 448–453, https://doi.org/10.1080/00365513.2017.1336569.
  119. Guido M., Roskams T., Pontisso P., Fassan M., Thung S.N., Giacomelli L., Sergio A., Farinati F., Cillo U., Rugge M. Squamous cell carcinoma antigen in human liver carcinogenesis. J Clin Pathol 2008; 61(4): 445–447, https://doi.org/10.1136/jcp.2007.051383.
  120. Anwar S.L., Lehmann U. MicroRNAs: emerging novel clinical biomarkers for hepatocellular carcinomas. J Clin Med 2015; 4(8): 1631–1650, https://doi.org/10.3390/jcm4081631.
  121. Cabiati M., Gaggini M., Cesare M.M., Caselli C., De Simone P., Filipponi F., Basta G., Gastaldelli A., Del Ry S. Osteopontin in hepatocellular carcinoma: a possible biomarker for diagnosis and follow-up. Cytokine 2017; 99: 59–65, https://doi.org/10.1016/j.cyto.2017.07.004.
  122. Hao C., Cui Y., Owen S., Li W., Cheng S., Jiang W.G. Human osteopontin: potential clinical applications in cancer (review). Int J Mol Med 2017; 39(6): 1327–1337, https://doi.org/10.3892/ijmm.2017.2964.
  123. Zhao H., Chen Q., Alam A., Cui J., Suen K.C., Soo A.P., Eguchi S., Gu J., Ma D. The role of osteopontin in the progression of solid organ tumour. Cell Death Dis 2018; 9(3): 356, https://doi.org/10.1038/s41419-018-0391-6.
  124. Bruha R., Jachymova M., Petrtyl J., Dvorak K., Lenicek M., Urbanek P., Svestka T., Vitek L. Osteopontin: a non-invasive parameter of portal hypertension and prognostic marker of cirrhosis. World J Gastroenterol 2016; 22(12): 3441–3450, https://doi.org/10.3748/wjg.v22.i12.3441.
  125. Fouad S.A., Mohamed N.A.G., Fawzy M.W., Moustafa D.A. Plasma osteopontin level in chronic liver disease and hepatocellular carcinoma. Hepat Mon 2015; 15(9): e30753, https://doi.org/10.5812/hepatmon.30753.
  126. Yahya S.M.M., Fathy S.A., El-Khayat Z.A., El-Toukhy S.E., Hamed A.R., Hegazy M.G.A., Nabih H.K. Possible role of microRNA-122 in modulating multidrug resistance of hepatocellular carcinoma. Indian J Clin Biochem 2018; 33(1): 21–30, https://doi.org/10.1007/s12291-017-0651-8.
  127. Lokman N.A., Ween M.P., Oehler M.K., Ricciardelli C. The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron 2011; 4(2): 199–208, https://doi.org/10.1007/s12307-011-0064-9.
  128. Tressler R.J., Updyke T.V., Yeatman T., Nicolson G.L. Extracellular annexin II is associated with divalent cation-dependent tumor cell-endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells. J Cell Biochem 1993; 53(3): 265–276, https://doi.org/10.1002/jcb.240530311.
  129. Díaz V.M., Hurtado M., Thomson T.M., Reventós J., Paciucci R. Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro. Gut 2004; 53(7): 993–1000, https://doi.org/10.1136/gut.2003.026831.
  130. Sharma M.R., Koltowski L., Ownbey R.T., Tuszynski G.P., Sharma M.C. Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol 2006; 81(2): 146–156, https://doi.org/10.1016/j.yexmp.2006.03.003.
  131. Shiozawa Y., Havens A.M., Jung Y., Ziegler A.M., Pedersen E.A., Wang J., Wang J., Lu G., Roodman G.D., Loberg R.D., Pienta K.J., Taichman R.S. Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 2008; 105(2): 370–380, https://doi.org/10.1002/jcb.21835.
  132. Lozada M.E., Chaiteerakij R., Roberts L.R. Screening for hepatocellular carcinoma and cholangiocarcinoma: can biomarkers replace imaging? Curr Hepatol Rep 2015; 14(2): 128–138, https://doi.org/10.1007/s11901-015-0261-y.
  133. Li J., Gong W., Li X., Wan R., Mo F., Zhang Z., Huang P., Hu Z., Lai Z., Lu X., Zhao Y. Recent progress of Wnt pathway inhibitor dickkopf-1 in liver cancer. J Nanosci Nanotechnol 2018; 18(8): 5192–5206, https://doi.org/10.1166/jnn.2018.14636.
  134. Zhou Y., Li W., Tseng Y., Zhang J., Liu J. Developing slow-off dickkopf-1 aptamers for early-diagnosis of hepatocellular carcinoma. Talanta 2019; 194: 422–429, https://doi.org/10.1016/j.talanta.2018.10.014.
  135. Pinato D.J., Mauri F.A., Lloyd T., Vaira V., Casadio C., Boldorini R.L., Sharma R. The expression of Axl receptor tyrosine kinase influences the tumour phenotype and clinical outcome of patients with malignant pleural mesothelioma. Br J Cancer 2013; 108(3): 621–628, https://doi.org/10.1038/bjc.2013.9.
  136. Axelrod H., Pienta K.J. Axl as a mediator of cellular growth and survival. Oncotarget 2014; 5(19): 8818–8852, https://doi.org/10.18632/oncotarget.2422.
  137. Byers L.A., Diao L., Wang J., Saintigny P., Girard L., Peyton M., Shen L., Fan Y., Giri U., Tumula P.K., Nilsson M.B., Gudikote J., Tran H., Cardnell R.J., Bearss D.J., Warner S.L., Foulks J.M., Kanner S.B., Gandhi V., Krett N., Rosen S.T., Kim E.S., Herbst R.S., Blumenschein G.R., Lee J.J., Lippman S.M., Ang K.K., Mills G.B., Hong W.K., Weinstein J.N., Wistuba I.I., Coombes K.R., Minna J.D., Heymach J.V. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res 2013; 19(1): 279–290, https://doi.org/10.1158/1078-0432.ccr-12-1558.
  138. D’Alfonso T.M., Hannah J., Chen Z., Liu Y., Zhou P., Shin S.J. Axl receptor tyrosine kinase expression in breast cancer. J Clin Pathol 2014; 67(8): 690–696, https://doi.org/10.1136/jclinpath-2013-202161.
  139. Dunne P.D., McArt D.G., Blayney J.K., Kalimutho M., Greer S., Wang T., Srivastava S., Ong C.W., Arthur K., Loughrey M., Redmond K., Longley D.B., Salto-Tellez M., Johnston P.G., Van Schaeybroeck S. AXL is a key regulator of inherent and chemotherapy-induced invasion and predicts a poor clinical outcome in early-stage colon cancer. Clin Cancer Res 2014; 20(1): 164–175, https://doi.org/10.1158/1078-0432.ccr-13-1354.
  140. Paccez J.D., Vogelsang M., Parker M.I., Zerbini L.F. The receptor tyrosine kinase Axl in cancer: biological functions and therapeutic implications. Int J Cancer 2014; 134(5): 1024–1033, https://doi.org/10.1002/ijc.28246.
  141. Hodeib H., ELshora O., Selim A., Sabry N.M., El-Ashry H.M. Serum midkine and osteopontin levels as diagnostic biomarkers of hepatocellular carcinoma. Electron Physician 2017; 9(1): 3492–3498, https://doi.org/10.19082/3492.
  142. Mashaly A.H., Anwar R., Ebrahim M.A., Eissa L.A., El Shishtawy M.M. Diagnostic and prognostic value of talin-1 and midkine as tumor markers in hepatocellular carcinoma in Egyptian patients. Asian Pac J Cancer Prev 2018; 19(6): 1503–1508.
  143. Lindner K., Gregán J., Montgomery S., Kearsey S.E. Essential role of MCM proteins in premeiotic DNA replication. Mol Biol Cell 2002; 13(2): 435–444, https://doi.org/10.1091/mbc.01-11-0537.
  144. Liu M., Hu Q., Tu M., Wang X., Yang Z., Yang G., Luo R. MCM6 promotes metastasis of hepatocellular carcinoma via MEK/ERK pathway and serves as a novel serum biomarker for early recurrence. J Exp Clin Cancer Res 2018; 37(1): 10, https://doi.org/10.1186/s13046-017-0669-z.
  145. Liu Z., Li J., Chen J., Shan Q., Dai H., Xie H., Zhou L., Xu X., Zheng S. MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression. BMC Cancer 2018; 18(1): 200, https://doi.org/10.1186/s12885-018-4056-8.
  146. Laurent T.C., Moore E.C., Reichard P. Enzymatic synthesis of deoxyribonucleotides. IV. Isolation and characterization of thioredoxin, the hydrogen donor from Escherichia Coli B. J Biol Chem 1964; 239: 3436–3444.
  147. Mollbrink A., Jawad R., Vlamis-Gardikas A., Edenvik P., Isaksson B., Danielsson O., Stål P., Fernandes A.P. Expression of thioredoxins and glutaredoxins in human hepatocellular carcinoma: correlation to cell proliferation, tumor size and metabolic syndrome. Int J Immunopathol Pharmacol 2014; 27(2): 169–183, https://doi.org/10.1177/039463201402700204.
  148. Gunes A., Bagirsakci E., Iscan E., Cakan-Akdogan G., Aykutlu U., Senturk S., Ozhan G., Erdal E., Nart D., Barbet F.Y., Atabey N. Thioredoxin interacting protein promotes invasion in hepatocellular carcinoma. Oncotarget 2018; 9(96): 36849–36866, https://doi.org/10.18632/oncotarget.26402.
  149. Cho S.Y., Kim S., Son M.J., Rou W.S., Kim S.H., Eun H.S., Lee B.S. Clinical significance of the thioredoxin system and thioredoxin-domain-containing protein family in hepatocellular carcinoma. Dig Dis Sci 2019; 64(1): 123–136, https://doi.org/10.1007/s10620-018-5307-x.
  150. Fox R., Berhane S., Teng M., Cox T., Tada T., Toyoda H., Kumada T., Kagebayashi C., Satomura S., Johnson P.J. Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model. Br J Cancer 2014; 110(8): 2090–2098, https://doi.org/10.1038/bjc.2014.130.
  151. Johnson P.J., Pirrie S.J., Cox T.F., Berhane S., Teng M., Palmer D., Morse J., Hull D., Patman G., Kagebayashi C., Hussain S., Graham J., Reeves H., Satomura S. The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers. Cancer Epidemiol Biomarkers Prev 2014; 23(1): 144–153, https://doi.org/10.1158/1055-9965.epi-13-0870.
  152. Berhane S., Toyoda H., Tada T., Kumada T., Kagebayashi C., Satomura S., Schweitzer N., Vogel A., Manns M.P., Benckert J., Berg T., Ebker M., Best J., Dechêne A., Gerken G., Schlaak J.F., Weinmann A., Wörns M.A., Galle P., Yeo W., Mo F., Chan S.L., Reeves H., Cox T., Johnson P. Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients. Clin Gastroenterol Hepatol 2016; 14(6): 875–886, https://doi.org/10.1016/j.cgh.2015.12.042.
  153. Kotha S., Neong S., Patel K. Serum biomarkers for diagnosis and monitoring viral hepatitis and hepatocellular carcinoma. Expert Rev Mol Diagn 2018; 18(8): 713–722, https://doi.org/10.1080/14737159.2018.1496020.
Malov S.I., Malov I.V., Dvornichenko V.V., Marche P.N., Decaens T., Macek-Jilkova Z., Yushchuk N.D. Biomarkers in Diagnosis and Prediction of Hepatocellular Carcinoma Recurrence (Review). Sovremennye tehnologii v medicine 2019; 11(2): 183, https://doi.org/10.17691/stm2019.11.2.23


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