The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+ pegylated interferon α-2b therapy against advanced hepatocellular carcinoma.
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.
Hagiwara
Satoru
S
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, Ōsakasayama, Osaka 589-8511, Japan.
Kudo
Masatoshi
M
Ueshima
Kazuomi
K
Chung
Hobyung
H
Yamaguchi
Mami
M
Takita
Masahiro
M
Haji
Seiji
S
Kimura
Masatomo
M
Arao
Tokuzo
T
Nishio
Kazuto
K
Park
Ah-Mee
AM
Munakata
Hiroshi
H
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D016158:Genes, p53; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010094:Oxonic Acid / Q000008:administration & dosage; D010455:Peptides / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011237:Predictive Value of Tests; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D004338:Drug Combinations; D006023:Glycoproteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C000606023:PROM1 protein, human; D010455:Peptides; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C120411:interferon receptor, type II; C079198:S 1 (combination); D005641:Tegafur; D011092:Polyethylene Glycols; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; C417083:peginterferon alfa-2b