title: A single nucleotide polymorphism on the GALNT14 gene as an effective predictor of response to chemotherapy in advanced hepatocellular carcinoma.
abstract: Previously, a pilot genome-wide association study has identified candidate single nucleotide polymorphism predictors for the therapeutic response of 5-fluorouracil, mitoxantrone and cisplatin (FMP) combination chemotherapy in advanced hepatocellular carcinoma (HCC). Here, we conducted a prospective confirmatory study to examine the predictive value of rs9679162 (located on GALNT14 gene) for the therapeutic responses using a split-dose FMP protocol. One hundred and seven advanced HCC patients receiving split-dose FMP therapy were enrolled. All patients were in Barcelona Clinical Liver Cancer Stage C with either main portal vein thrombosis and/or distant metastasis. Of them, 105 (98.1%) were Child-Pugh classification B. GALNT14 genotype was determined before therapy. Of the patients included, 28 were rs9679162 "TT" and 79 were "non-TT" ("GG" + "GT") genotype. The median overall survival, time-to-progression, response rate and disease control rate were ("TT" versus "non-TT") 6.8 versus 3.9 months (p < 0.001), 3.9 versus 2.1 months (p < 0.001), 28.6% versus 10.1% (p = 0.029) and 35.7% versus 15.2% (p = 0.030), respectively. Multivariate analysis indicated that rs9679162 genotype was an independent predictor for overall survival (p = 0.002). Categorical analysis showed that 17 patients with "TT" genotype, tumor size < 10 cm and neutrophils < 74% had a median overall survival of 25.5 months and a therapeutic response rate of 47.1%. In conclusion, this prospective study confirmed that GALN14 genotype (rs9679162) was an effective predictor for therapeutic outcome in advanced HCC patients treated by FMP chemotherapy. Combining GALNT14 genotype and clinical parameters, a subgroup of patients with excellent outcome was identified.
authors: Liver Research Unit, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Taipei, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors: Chau-Ting
authors: CT
authors: Yeh
authors: Kung-Hao
authors: KH
authors: Liang
authors: Chen-Chun
authors: CC
authors: Lin
authors: Ming-Ling
authors: ML
authors: Chang
authors: Cheng-Lung
authors: CL
authors: Hsu
authors: Chien-Fu
authors: CF
authors: Hung
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D009503:Neutropenia / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D016685:Mitomycin; D017350:N-Acetylgalactosaminyltransferases; D002945:Cisplatin; D005472:Fluorouracil
keywords: chemotherapy; hepatocellular carcinoma; response# mitoxantrone; single nucleotide polymorphism