Serum tumor markers and their prognostic value in Turkish hepatocellular cancer patients
Serum tumor markers and their prognostic value in Turkish hepatocellular cancer patients
Aim: Association between serum tumor markers and hepatocellular cancer (HCC) patients' survival has been investigating for decades. Despite glypican 3 has been reported superior to AFP in predicting the prognosis of HCC patients recently, the prognostic value of glypican 3 not clear. We aimed to investigate the prognostic value of serum glypican 3 and its relationship with the characteristic features in the Turkish HCC patients' cohort.Material and Methods: A total of 84 HCC patients were enrolled prospectively. Serum glypican 3 levels were analyzed and serum levels of glypican 3 were compared according to many different types of the clinicopathologic features of HCC.Results: A total of 84 patients, 71 of the patients were male and 13 were female. There were 36 hepatitis B (HBV) and 8 hepatitis C (HCV) infected patients. Forty-eight patients had cirrhosis and 35 patients did not. Serum glypican 3 levels were lower in cirrhotic than non-cirrhotic patients (p =0.6). Difference between overall survival (OS) of patients with serum glypican 3 levels ≥ 2 ng/mL and patient with serum glypican 3 level < 2 ng/mL was not significant, the OS estimates were 7.8 and 6.1 months, respectively (p=0.3). The median OS was 7.38 months. There was a positive correlation between serum AFP level and glypican 3, but not statistically significant (p=0.07). Conclusion: The study results indicate that serum glypican 3 level is elevated in HCC patients with poorer features. Therefore, despite nonsignificant results, the method that contains the prediction of HCC patients' survival by serum glypican 3 level needs to be clarified with larger trials.
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- 1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:359-86.
- 2. Akinyemiju T, Abera S, Ahmed M, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncology 2017;3:1683-91.
- 3. Ryerson AB, Eheman CR, Altekruse SF, et al. Annual Report to the Nation on the Status of Cancer, 1975- 2012, featuring the increasing incidence of liver cancer. Cancer 2016;122:1312-37.
- 4. Pham C, Fong TL, Zhang J, et al. Striking Racial/ Ethnic Disparities in Liver Cancer Incidence Rates and Temporal Trends in California, 1988-2012. J Natl Cancer Inst 2018;110:1259-69.
- 5. Chen DS, Sung JL, Sheu JC, et al. Serum alphafetoprotein in the early stage of human hepatocellular carcinoma. Gastroenterology 1984;86:1404-9.
- 6. Marrero JA, Su GL, Wei W, et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients. Hepatology 2003;37:1114-21.
- 7. Toyoda H, Kumada T, Tada T, et al. Clinical utility of highly sensitive Lens culinaris agglutinin-reactive alpha-fetoprotein in hepatocellular carcinoma patients with alpha-fetoprotein <20 ng/mL. Cancer Sci 2011;102:1025-31.
- 8. Filmus J, Capurro M. Glypican-3 and alphafetoprotein as diagnostic tests for hepatocellular carcinoma. Mol Diagn 2004;8:207-12.
- 9. Bai DS, Zhang C, Chen P, et al. The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma. Sci Rep 2017;7:12870.
- 10. Matsumoto Y, Suzuki T, Asada I, et al. Clinical classification of hepatoma in Japan according to serial changes in serum alpha-fetoprotein levels. Cancer 1982;49:354-60.
- 11. Kojiro M, Wanless I, Alves V, et al. Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology 2009;49:658-64.
- 12. Libbrecht L, Severi T, Cassiman D, et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol 2006;30:1405-11.
- 13. Yao M, Yao DF, Bian YZ, et al. Values of circulating GPC-3 mRNA and alpha-fetoprotein in detecting patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2013;12:171-9.
- 14. Zhou F, Shang W, Yu X, et al. Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med Res Rev 2018;38:741-67.
- 15. Amin MB, Edge SB. AJCC cancer staging manual: springer; 2017.
- 16. Poon RT, Fan ST, Lo CM, et al. Long-term prognosis after resection of hepatocellular carcinoma associated with hepatitis B-related cirrhosis. J Clin Oncol 2000;18:1094-101.
- 17. Hsu CY, Liu PH, Lee YH, et al. Using serum alphafetoprotein for prognostic prediction in patients with hepatocellular carcinoma: what is the most optimal cutoff? PLoS One. 2015;10:0118825.
- 18. Schutte K, Schulz C, Link A, et al. Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis. World J Hepatol 2015;7:139-49.
- 19. Feng J, Zhu R, Chang C, et al. CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection. PLoS One 2016;11:e0151501.
- 20. Filmus J, Capurro M, Rast J. Glypicans. Genome Biol. 2008;9:224.
- 21. Yorita K, Takahashi N, Takai H, et al. Prognostic significance of circumferential cell surface immunoreactivity of glypican-3 in hepatocellular carcinoma. Liver Int 2011;31:120-31.
- 22. Shirakawa H, Suzuki H, Shimomura M, et al. Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma. Cancer Sci 2009;100:1403-7.
- 23. Haruyama Y, Yorita K, Yamaguchi T, et al. High preoperative levels of serum glypican-3 containing N-terminal subunit are associated with poor prognosis in patients with hepatocellular carcinoma after partial hepatectomy. Int J Cancer 2015;137:1643-51.
- 24. Schöniger-Hekele M, Müller C, Kutilek M, et al. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut 2001;48:103-9.
- 25. Llovet J M, Bustamante J, Castells A, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999;29:62-7.
- 26. Hwang S, Lee YJ, Kim KH, et al. The Impact of Tumor Size on Long-Term Survival Outcomes After Resection of Solitary Hepatocellular Carcinoma: Single-Institution Experience with 2558 Patients. J Gastrointest Surg 2015;19:1281-90.
- 27. Huang WJ, Jeng YM, Lai HS, et al. Tumor size is a major determinant of prognosis of resected stage I hepatocellular carcinoma. Langenbecks Arch Surg 2015;400:725-34.
- 28. Wu G, Wu J, Wang B, et al. Importance of tumor size at diagnosis as a prognostic factor for hepatocellular carcinoma survival: a population-based study. Cancer Manag Res 2018;10:4401-10.
- 29. Nomura F, Ohnishi K, Tanabe Y. Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients. Cancer 1989;64:1700-7.
- 30. Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985;56:918- 28.
- 31. Llovet JM, Bruix J. Prospective validation of the Cancer of the Liver Italian Program (CLIP) score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000;32:679- 80.
- 32. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329-38.
- 33. Chen M, Li G, Yan J, et al. Reevaluation of glypican-3 as a serological marker for hepatocellular carcinoma. Clin Chim Acta 2013;423:105-11.
- 34. Liu H, Li P, Zhai Y, et al. Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol 2010;16:4410-5.
- 35. Qiao SS, Cui Z Q, Gong L, et al. Simultaneous measurements of serum AFP, GPC-3 and HCCR for diagnosing hepatocellular carcinoma. Hepatogastroenterology 2011;58:1718-24.
- 36. Tangkijvanich P, Chanmee T, Komtong S, et al. Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers. J Gastroenterol Hepatol 2010;25:129-37.
- 37. Lee HJ, Yeon JE, Suh SJ, et al. Clinical utility of plasma glypican-3 and osteopontin as biomarkers of hepatocellular carcinoma. Gut Liver 2014;8:177-85.