The Expressions of CD44, CD90 and Alpha Fetoprotein Biomarkers in Indonesian Patients with Advanced Liver Disease: an Observational Study

Syifa Mustika, Hengki Wijaya, Bogi Pratomo

Abstract


Background: increased serum alpha fetoprotein (AFP) levels are often found in patients with advanced hepatocellular carcinoma (HCC). Cluster Differentiation 44 (CD44) and CD90 are stem cell biomarkers that have been assumed as the early HCC markers and associated with onset and progressivity of HCC. The study related to HCC stem cell has not been available in Indonesia. The present study aimed to evaluate the expression of cancer stem cell markers (CD44, CD90) and AFP levels in patients with advanced liver disease. Methods: an observational study was conducted in 41 patients with chronic hepatitis B and/or C infection, liver cirrhosis, and HCC at dr. Saiful Anwar General Hospital. CD44 and CD90 expressions were measured with flow cytometry, and AFP serum levels with ELISA. Data on patient characteristics were evaluated using bivariate and multivariate statistical analysis (One-way ANOVA, Mann-Whitney, Chi-Square, Kruskal-Wallis). Data of CD44, CD90 and AFP were analyzed using Kruskal Wallis test with a significance value of p<0.05, and diagnostic power was analyzed using receiver operating characteristic (ROC). Results: the subjects of our study were 16 patients with chronic hepatitis, 15 patients with liver cirrhosis, and 10 patients with HCC. There was a significant difference regarding CD44+CD90+ and AFP among those three groups (p=0.001; p=0.000) specifically in chronic hepatitis compared to liver cirrhosis (p=0.002; p=0.000) and HCC (p=0.002; p=0.000) respectively. ROC analysis showed the best diagnostic power for the combination of CD44+CD90+ and AFP (AUC=0.981; p=0.000). Conclusion: there are higher expressions of CD44+CD90+ and serum AFP levels in patients with HCC compared to the other two groups (those with chronic hepatitis and liver cirrhosis). The combination of both parameters has the best diagnostic power of HCC.

Keywords


AFP; Biomarker; Chronic Hepatitis; liver cirrhosis; HCC

References


Yamashita T, Wang XW. Cancer stem cells in the development of liver cancer. J Clin Invest. 2013;123(5):1911-1918.

Salkinov AV, Kusumawidjaja G, Rausch V, et al. Cancer stem cell marker expression in hepatocellular carcinoma and liver metastases is not sufficient as single prognostic parameter. Cancer Lett. 2009:275(2):185-93.

Sinn DH, Yi J, Choi MS, et al. Incidence and risk factors for surveillance failure in patients with regular hepatocellular carcinoma surveillance. Hepatol Int. 2013;7(4):1010-8.

Schinzari V, Barnaba V, Piconese S. Chronic hepatitis B virus and hepatitis C virus infections and cancer: synergy between viral and host factors. Clin Microbiol Infect 2015;21:969–74.

Verma M, Maruvada P, Srivastava S. Epigenetics and Cancer. Crit Rev Clin Lab Sci. 2004;41:585–607.

Bruix J, Sherman M. American Association for the Study of Liver Disease. Management of hepatocellular carcinoma: an update. Hepatology. 2011:53(3):1020-2.

Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4(2):439-74.

Tzartzeva K, Obi J, Rich NE, Marrero JA, Yopp A, Waljee A, Singal AG. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: A meta-analysis. Gastroenterology. 2018;154:1706–18.

Yoshida M, Yamashita T, Okada H, et al. Sorafenib suppresses extrahepatic metastasis de novo in hepatocellular carcinoma through inhibition of mesenchymal cancer stem cells characterized by the expression of CD90. Scientific Reports. 2017;7(1):11292.

Shiota N, Itaba N. Progress in stem cell-based therapy for liver disease. Hepatology Research. 2017;47:127-41.

Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cells. 2008;13(2):153-66.

Shen-hua X. Ming Z, Jian-guo F, et al. Significance of CD44 in the peripheral blood of patients with gastric cancer. Chinese J Cancer Res. 2001;13(3):226-7.

Fujita T. Subpopulations of circulating cancer stem cell-like cells. Annals of Surgery. 2014;259(3):e53.

Naor D, Nedvetzki S, Golan I, et al. CD44 in cancer. Crit Rev Clin Lab Sci. 2002;39(6):527-79.

Jaggupilli A, Elkord E. Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol. 2012;2012:708036.

Sun JH, Luo Q, Liu LL, et al. Liver cancer stem cell markers: Progression and therapeutic implications. World J Gastroenterol. 2016;22(13):3547-57.

Yang ZF, Ngai P, Ho DW, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 2008;47(3):919-928.

Romano M, De Francesco F, Pirozzi G, et al. Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma. Oncoscience. 2015;2(5):443-56.

Marrero JA, Fontana RJ, Barrat A, et al. Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort. Hepatology. 2005;41(4):707-15.

Jang ES, Jeong S-H, Kim J-W, Choi YS, Leissner P, Brechot C (2016) diagnostic performance of alpha-fetoprotein, protein induced by vitamin K absence, osteopontin, Dickkopf-1 and its combinations for hepatocellular carcinoma. PLoS ONE 11(3): e0151069. doi:10.1371/journal.pone.0151069.

Gani RA, Suryamin M, Hasan I, Lesmana RA, Sanityoso A. Performance of alpha fetoprotein in combination with alpha-1-acid glycoprotein for diagnosis of hepatocellular carcinoma among liver cirrhosis patients. Acta Med Indones - Indones J Intern Med. 2015;47(3):216-22.

Liu R, Shen Y, Nan K, Mi B, Wu T, Guo J, et al. Association between expression of cancer stem cell markers and poor differentiation of hepatocellular carcinoma: Meta-analysis. Medicine (Baltimor). 2015;94(31):1306-15.

Wilson GS, Hu Z, Duan W, et al. Efficacy of using cancer stem cell markers in isolating and characterizing liver cancer stem cells. Stem Cells Dev. 2013;22(19):2255-664.


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