TY - JOUR
T1 - Combinations of single nucleotide polymorphisms WWOX-rs13338697, GALNT14-rs9679162 and rs6025211 effectively stratify outcomes of chemotherapy in advanced hepatocellular carcinoma
AU - Lin, Wey Ran
AU - Hsu, Chao Wei
AU - Yeh, Christopher Sung Huan
AU - Chen, Yi Cheng
AU - Chang, Ming Ling
AU - Liang, Kung Hao
AU - Lin, Chen Chun
AU - Chu, Yu De
AU - Yeh, Chau Ting
N1 - Publisher Copyright:
© 2017 John Wiley & Sons Australia, Ltd
PY - 2018/4
Y1 - 2018/4
N2 - Aim: A genome-wide association study (GWAS) had identified a single nucleotide polymorphism (SNP), GALNT14-rs9679162, capable of predicting chemotherapy responses in advanced hepatocellular carcinoma (HCC). Here, we revisited the GWAS database to search for necessary SNPs that could improve our outcome prediction. Methods: A cohort of 116 HCC patients receiving split-dose chemotherapy composed of 5-fluorouracil, mitoxantrone and cisplatin was enrolled. The GALNT14-rs9679162 together with four other leading candidate SNPs (rs6025211, rs715171, LOC105369482-rs1955024 and WWOX-rs13338697) was genotyped and correlated with time-to-tumor progression (TTP) and overall survival (OS). Results: GALNT14-rs9679162-TT genotype remained an effective predictor for favorable TTP and OS (P = 0.012 and 0.002). Additionally, it was found that WWOX-rs13338697-CT genotype was associated with unfavorable TTP (P = 0.031), independent of GALNT14-rs9679162 genotype (adjusted P = 0.045), and rs6025211-CT genotype was associated with unfavorable OS (P = 0.014), independent of GALNT14-rs9679162 genotype (adjusted P = 0.025). Combinations of these SNPs stratified patients into three groups with differential treatment outcomes. Patients with GALNT14-rs9679162-TT/WWOX-rs13338697-non-CT genotypes achieved the most favorable treatment outcomes (n = 19; median TTP, median OS and response rate were 3.9 months, 6.8 months and 4/19 [21.1%], respectively); whereas patients with GALNT14-rs9679162-non-TT/rs6025211-CT genotypes associated with the most unfavorable treatment outcomes (n = 40; median TTP, median OS and response rate were 1.9 months, 3.5 months and 1/40 [2.5%], respectively). The remaining patients constituted a third subgroup with intermediate clinical outcomes. Conclusions: Three genetic variants, GALNT14-rs9679162, WWOX-rs13338697 and rs6025211, stratified advanced HCC patients into three groups with differential treatment outcomes.
AB - Aim: A genome-wide association study (GWAS) had identified a single nucleotide polymorphism (SNP), GALNT14-rs9679162, capable of predicting chemotherapy responses in advanced hepatocellular carcinoma (HCC). Here, we revisited the GWAS database to search for necessary SNPs that could improve our outcome prediction. Methods: A cohort of 116 HCC patients receiving split-dose chemotherapy composed of 5-fluorouracil, mitoxantrone and cisplatin was enrolled. The GALNT14-rs9679162 together with four other leading candidate SNPs (rs6025211, rs715171, LOC105369482-rs1955024 and WWOX-rs13338697) was genotyped and correlated with time-to-tumor progression (TTP) and overall survival (OS). Results: GALNT14-rs9679162-TT genotype remained an effective predictor for favorable TTP and OS (P = 0.012 and 0.002). Additionally, it was found that WWOX-rs13338697-CT genotype was associated with unfavorable TTP (P = 0.031), independent of GALNT14-rs9679162 genotype (adjusted P = 0.045), and rs6025211-CT genotype was associated with unfavorable OS (P = 0.014), independent of GALNT14-rs9679162 genotype (adjusted P = 0.025). Combinations of these SNPs stratified patients into three groups with differential treatment outcomes. Patients with GALNT14-rs9679162-TT/WWOX-rs13338697-non-CT genotypes achieved the most favorable treatment outcomes (n = 19; median TTP, median OS and response rate were 3.9 months, 6.8 months and 4/19 [21.1%], respectively); whereas patients with GALNT14-rs9679162-non-TT/rs6025211-CT genotypes associated with the most unfavorable treatment outcomes (n = 40; median TTP, median OS and response rate were 1.9 months, 3.5 months and 1/40 [2.5%], respectively). The remaining patients constituted a third subgroup with intermediate clinical outcomes. Conclusions: Three genetic variants, GALNT14-rs9679162, WWOX-rs13338697 and rs6025211, stratified advanced HCC patients into three groups with differential treatment outcomes.
KW - chemotherapy
KW - hepatocellular carcinoma
KW - prognosis
KW - single nucleotide polymorphism
UR - https://www.scopus.com/pages/publications/85022182028
U2 - 10.1111/ajco.12745
DO - 10.1111/ajco.12745
M3 - 文章
C2 - 28695683
AN - SCOPUS:85022182028
SN - 1743-7555
VL - 14
SP - e54-e63
JO - Asia-Pacific Journal of Clinical Oncology
JF - Asia-Pacific Journal of Clinical Oncology
IS - 2
ER -
