title: GALNT14genotype, α-fetoprotein and therapeutic side effects predict post-chemotherapy survival in patients with advanced hepatocellular carcinoma.
abstract: In addition to targeted agents, chemotherapy is currently considered to be a treatment option for patients with advanced hepatocellular carcinoma (HCC); however, it is associated with severe side effects that may limit its clinical use. UDP-N-acetyl-α-D-galactosamine:polypeptideN-acetyl-galactosaminyltransferase 14 (GALNT14) genotype was previously identified as a prognostic marker for HCC patients receiving 5-fluorouracil, mitoxantrone and cisplatin (FMP) combination chemotherapy. The present study aimed to assess clinical parameters and on-treatment side effects as effective predictors for favorable prognosis. A total of 118 patients with HCC receiving split-dose FMP were retrospectively enrolled. The clinical parameters, side effects andGALNT14genotype were analyzed. The independent predictors for time-to-progression (TTP) and overall survival (OS) were assessed using Cox proportional hazards models. Following categorization, the Kaplan-Meier method was used to compare survival outcomes. Pretreatment α-fetoprotein (AFP) ≤2,800 ng/ml (median level),GALNT14'TT' genotype, on-treatment leukopenia and absence of vomiting were identified as independent predictors of a favorable TTP (P=0.001, 0.035, 0.008 and 0.009, respectively) and OS (P=0.028, 0.006, 0.027 and 0.013, respectively). A total of 59 patients with AFP ≤2,800 ng/ml exhibited longer median TTP and OS (3.11 vs. 1.75 months, P<0.001; and 8.14 vs. 3.79 months, P<0.001, respectively). A total of 30 patients with theGALNT14'TT' genotype exhibited longer median TTP and OS (3.11 vs. 2.11 months, P=0.014; and 5.75 vs. 3.93 months, P=0.001, respectively). Finally, 9 patients (9/118; 7.6%) with all four favorable factors exhibited the longest median TTP and OS (10.64 vs. 2.07 months, P=0.002; and 25.50 vs. 4.50 months, P<0.001, respectively). In conclusion, the AFP level and theGALNTgenotype may be considered as pre-therapeutic predictors of a favorable response. When combined with on-treatment leukopenia and absence of vomiting, a subgroup of patients with excellent outcome may be identified.
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, R.O.C. ; Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Wey-Ran
authors.initials: WR
authors.lastname: Lin
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, R.O.C. ; Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hsu
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, R.O.C. ; Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, R.O.C. ; Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Chang
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Kung-Hao
authors.initials: KH
authors.lastname: Liang
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, R.O.C. ; Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, R.O.C. ; Chang Gung University College of Medicine, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
keywords: chemotherapy; hepatocellular carcinoma; response; single-nucleotide polymorphism; α-fetoprotein