PLCE1 Polymorphisms and Expression Combined with Serum AFP Level Predicts Survival of HBV-related Hepatocellular Carcinoma Patients After Hepatectomy

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Apr 19

PMID 28418898

Citations 3

Authors

Xiwen Liao

Chuangye Han

Wei Qin

Xiaoguang Liu

Long Yu

Guangzhi Zhu

Tingdong Yu

Sicong Lu

Hao Su

Zhen Liu

Zhiwei Chen

Chengkun Yang

Ketuan Huang

Zhengtao Liu

Yu Liang

Jianlu Huang

Jiahong Dong

Lequn Li

Xue Qin

Xinping Ye

Kaiyin Xiao

Minhao Peng

Tao Peng

Affiliations

Soon will be listed here.

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.

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References

Qi L, Bai T, Chen Z, Wu F, Chen Y, De Xiang B . The p53 mutation spectrum in hepatocellular carcinoma from Guangxi, China : role of chronic hepatitis B virus infection and aflatoxin B1 exposure. Liver Int. 2014; 35(3):999-1009. DOI: 10.1111/liv.12460. View

Bruix J, Sherman M . Management of hepatocellular carcinoma: an update. Hepatology. 2011; 53(3):1020-2. PMC: 3084991. DOI: 10.1002/hep.24199. View

Xu L, Qian G, Tang L, Su J, Wang J . Genetic variations of hepatitis B virus and serum aflatoxin-lysine adduct on high risk of hepatocellular carcinoma in Southern Guangxi, China. J Hepatol. 2010; 53(4):671-6. PMC: 6022746. DOI: 10.1016/j.jhep.2010.04.032. View

Cui X, Chen Y, Pang X, Liu W, Hu J, Li S . Multiple polymorphisms within the PLCE1 are associated with esophageal cancer via promoting the gene expression in a Chinese Kazakh population. Gene. 2013; 530(2):315-22. DOI: 10.1016/j.gene.2013.08.057. View

Ou L, Guo Y, Luo C, Wu X, Zhao Y, Cai X . RNA interference suppressing PLCE1 gene expression decreases invasive power of human bladder cancer T24 cell line. Cancer Genet Cytogenet. 2010; 200(2):110-9. DOI: 10.1016/j.cancergencyto.2010.01.021. View

Zhu M, Lu Y, Li W, Guo J, Dong X, Lin B . Hepatitis B Virus X Protein Driven Alpha Fetoprotein Expression to Promote Malignant Behaviors of Normal Liver Cells and Hepatoma Cells. J Cancer. 2016; 7(8):935-46. PMC: 4910586. DOI: 10.7150/jca.13628. View

Stanaway J, Flaxman A, Naghavi M, Fitzmaurice C, Vos T, Abubakar I . The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet. 2016; 388(10049):1081-1088. PMC: 5100695. DOI: 10.1016/S0140-6736(16)30579-7. View

Jia X, Liu P, Zhang M, Feng T, Tang H, Tang Z . Genetic variants at 6p21, 10q23, 16q21 and 22q12 are associated with esophageal cancer risk in a Chinese Han population. Int J Clin Exp Med. 2016; 8(10):19381-7. PMC: 4694479. View

Luo X . Phospholipase C ε-1 inhibits p53 expression in lung cancer. Cell Biochem Funct. 2013; 32(3):294-8. DOI: 10.1002/cbf.3015. View

10.

Yang J, Wu H, Wei S, Xiong H, Fu X, Qi Z . HPV seropositivity joints with susceptibility loci identified in GWASs at apoptosis associated genes to increase the risk of Esophageal Squamous Cell Carcinoma (ESCC). BMC Cancer. 2014; 14:501. PMC: 4227071. DOI: 10.1186/1471-2407-14-501. View

11.

Umar M, Upadhyay R, Kumar S, Ghoshal U, Mittal B . Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population. Tumour Biol. 2014; 35(11):11667-76. DOI: 10.1007/s13277-014-2458-z. View

12.

Wu C, Hu Z, He Z, Jia W, Wang F, Zhou Y . Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Nat Genet. 2011; 43(7):679-84. DOI: 10.1038/ng.849. View

13.

Zhu H, Yang M, Zhang H, Chen X, Yang X, Zhang C . Genome-wide association pathway analysis to identify candidate single nucleotide polymorphisms and molecular pathways for gastric adenocarcinoma. Tumour Biol. 2015; 36(7):5635-9. DOI: 10.1007/s13277-015-3236-2. View

14.

Duan F, Xie W, Cui L, Wang P, Song C, Qu H . Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: based on published genome-wide association studies in a central Chinese population. Cancer Epidemiol. 2013; 37(5):647-52. DOI: 10.1016/j.canep.2013.04.009. View

15.

Hu H, Yang J, Sun Y, Yang Y, Qian J, Jin L . Putatively functional PLCE1 variants and susceptibility to esophageal squamous cell carcinoma (ESCC): a case-control study in eastern Chinese populations. Ann Surg Oncol. 2011; 19(7):2403-10. DOI: 10.1245/s10434-011-2160-y. View

16.

Stolzel F, Pfirrmann M, Aulitzky W, Kaufmann M, Bodenstein H, Bornhauser M . Risk stratification using a new prognostic score for patients with secondary acute myeloid leukemia: results of the prospective AML96 trial. Leukemia. 2010; 25(3):420-8. DOI: 10.1038/leu.2010.279. View

17.

Qu Y, Zhang S, Cui L, Wang K, Song C, Wang P . Two novel polymorphisms in PLCE1 are associated with the susceptibility to esophageal squamous cell carcinoma in Chinese population. Dis Esophagus. 2016; 30(1):1-7. DOI: 10.1111/dote.12463. View

18.

Olivier M, Hollstein M, Hainaut P . TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010; 2(1):a001008. PMC: 2827900. DOI: 10.1101/cshperspect.a001008. View

19.

Li Y, An J, Huang S, Liao H, Weng Y, Cai S . PLCE1 suppresses p53 expression in esophageal cancer cells. Cancer Invest. 2014; 32(6):236-40. DOI: 10.3109/07357907.2014.905588. View

20.

Zhu M, Guo J, Li W, Lu Y, Fu S, Xie X . Hepatitis B virus X protein induces expression of alpha-fetoprotein and activates PI3K/mTOR signaling pathway in liver cells. Oncotarget. 2015; 6(14):12196-208. PMC: 4494932. DOI: 10.18632/oncotarget.2906. View