PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy

作者:Liao, Xiwen; Han, Chuangye; Qin, Wei; Liu, Xiaoguang; Yu, Long; Zhu, Guangzhi; Yu, Tingdong; Lu, Sicong; Su, Hao; Liu, Zhen; Chen, Zhiwei; Yang, Chengkun; Huang, Ketuan; Liu, Zhengtao; Liang, Yu; Huang, Jianlu; Dong, Jiahong; Li, Lequn; Qin, Xue; Ye, Xinping; Xiao, Kaiyin; Peng, Minhao; Peng, Tao*
来源:Oncotarget, 2017, 8(17): 29202-29219.
DOI:10.18632/oncotarget.16346

摘要

Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in the development and progression of several types of cancer. The present study investigated the prognostic significance of PLCE1 gene polymorphisms and expression combined with serum a-fetoprotein (AFP) level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms were genotyped by sequencing DNA isolated from surgically resected tumor samples of 421 HBVrelated HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (A(rs2274223)C(rs3765524); G(rs2274223)T(rs3765524)) with AFP level stratified at 20 ng/ml showed a significant association with overall survival(OS) of HBV-related HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP level >= 20 ng/ml had an increased risk of death as compared to those with the AC haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively). Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased risk of death, although with a non-significant P value (adjusted P=0.092). Joint-effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300 ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and expression combined with serum AFP level may predict postoperative outcome of HBV-related HCC patients.