Abstract
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 α-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 HBV-related HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (Ars2274223Crs3765524; Grs2274223Trs3765524) 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.
Highlights
RESULTSEastern Asia has the highest incidence of liver cancer in the world [1]
We found that phospholipase C epsilon 1 (PLCE1) haplotypes were not associated with overall survival (OS) according to this stratification
PLCE1 is a member of phosphoinositide-specific PLC family that serves as a link between the second messengers and small GTPases and regulates some Ras family members [34, 35]
Summary
Hepatitis B virus (HBV) infection has a high prevalence (> 5%) in the Chinese population [2, 3], and in 2012, more than half of new cases of liver cancer and death from the disease occurred in China [1]. Liver cancer is the third leading cause of cancer-related death in China [4], with an age-standardized 5-year relative survival rate of 10.1% [5]. Most of these are cases of hepatocellular carcinoma(HCC) [6]. The population in Guangxi is suitable for exploring the relationship between AFB1 exposure, HBV infection, TP53 codon 249 mutation, and HCC
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