The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+ pegylated interferon α-2b therapy against advanced hepatocellular carcinoma

• Published in: Journal of gastroenterology 2011-02, Vol.46 (2), p.212-221
• Main Authors: Hagiwara, Satoru, Kudo, Masatoshi, Ueshima, Kazuomi, Chung, Hobyung, Yamaguchi, Mami, Takita, Masahiro, Haji, Seiji, Kimura, Masatomo, Arao, Tokuzo, Nishio, Kazuto, Park, Ah-Mee, Munakata, Hiroshi
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; AC133 Antigen; Adult; Aged; Aged, 80 and over; Antigens, CD - metabolism; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor agents; Biliary Tract; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Colorectal Surgery; Dihydrouracil Dehydrogenase (NADP) - metabolism; Disease-Free Survival; Drug Combinations; Female; Gastroenterology; Genes, p53; Glycoproteins - metabolism; Hepatocellular carcinoma; Hepatology; Humans; Interferon; Interferon-alpha - administration & dosage; Kaplan-Meier Estimate; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Original Article—Liver; Oxonic Acid - administration & dosage; p53 Protein; Pancreas; Peptides - metabolism; Polyethylene Glycols - administration & dosage; Predictive Value of Tests; Protein expression; Proteins; Receptors, Interferon - metabolism; Recombinant Proteins; Stem cells; Surgical Oncology; Survival Rate; Tegafur - administration & dosage; Thymidylate synthase; Thymidylate Synthase - metabolism; Treatment Outcome; α-Interferon
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-010-0294-5

Background Combination therapy with the oral fluoropyrimidine anticancer drug S1 and interferon is reportedly effective for the treatment of advanced hepatocellular carcinoma (HCC), but selection criteria for this therapy have not been clarified. In this study, we attempted to identify factors predicting the effectiveness of this combination therapy. Methods Pathological specimens of HCC were collected before treatment from 31 patients with advanced HCC who underwent S1+ pegylated-interferon (PEG-IFN) α-2b therapy between January 2007 and January 2009. In these pathological specimens, the expression levels of CD133, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and interferon-receptor 2 (IFNR2) proteins were determined by Western blot assay. The presence or absence of p53 gene mutations was determined by direct sequencing. The relationships between these protein expression levels and the response rate (RR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results The CD133 protein expression level was significantly lower in the responder group than in the nonresponder group. Comparing the PFS and OS between high- and low-level CD133 expression groups ( n  = 13 and 18, respectively) revealed that both parameters were significantly prolonged in the latter group. The expression levels of TS, DPD, and IFNR2 protein and the presence of p53 gene mutations did not correlate with the RR. Conclusions CD133 was identified as a predictor of the therapeutic effect of S1+ PEG-IFN α-2b therapy against advanced HCC.