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

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 ?-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.

SUBMITTER: Liao X

PROVIDER: S-EPMC5438724 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Liao Xiwen X Han Chuangye C Qin Wei W Liu Xiaoguang X Yu Long L Zhu Guangzhi G Yu Tingdong T Lu Sicong S Su Hao H Liu Zhen Z Chen Zhiwei Z Yang Chengkun C Huang Ketuan K Liu Zhengtao Z Liang Yu Y Huang Jianlu J Dong Jiahong J Li Lequn L Qin Xue X Ye Xinping X Xiao Kaiyin K Peng Minhao M Peng Tao T

Oncotarget 20170401 17

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 patient ...[more]

PMID: 28418898

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Project description:BackgroundAlpha-fetoprotein (AFP), routinely used for diagnosis of hepatocellular carcinoma (HCC), is limited with relatively low sensitivity and high false positivity in HBV-related HCC (HBV-HCC). Thus, an alternative approach was explored to improve specificity/sensitivity for diagnosis of HBV-HCC, using the combination of AFP, inflammatory score, and liver function.MethodsChronic hepatitis B (CHB) (n = 510) and HBV-HCC (n = 473) patients were identified retrospectively for this study. The diagnostic value of single vs combined biomarkers for HBV-HCC was analyzed, using ROC curve.ResultsIt was observed that elderliness, male sex, cirrhosis, HBeAg+ or no-antiviral therapy, and elevation of ALT, AST, neutrophil-lymphocyte ratio (NLR), and AFP were associated with developing HBV-HCC. However, the cut-off ALT defined by Chinese standard, but not by AASLD, was a risk factor. Interestingly, AFP of HBeAg- HBV-HCC patients without cirrhosis was significantly higher than that of the HBeAg+ patients. AUC values for AFP, ALT, AST, or NLR were 0.84 (95% CI: 0.815-0.862), 0.533 (95% CI: 0.501-0.565), 0.696 (95% CI: 0.666-0.725), or 0.684 (95% CI: 0.654-0.713) with optimal cut-off at 7.21 ng/mL, 43 IU/mL, 38 IU/mL, or 2.61, respectively. Combination of AFP with ALT, AST, and NLR improved the diagnostic performance for HBV-HCC, compared to any of the single biomarkers or any other combinations among these patients (except no-cirrhosis).ConclusionsElderliness, male sex, elevated ALT, AST, NLR, AFP, cirrhosis, HBeAg+ , and no-antiviral treatment were independent risk factors for HBV-HCC. AASLD standard of ALT cut-off value may not be suitable for the Chinese population. Regular monitoring of HCC among HBeAg- patients with abnormal AFP may improve the management of HBV-HCC. The diagnostic performance of AFP combined with ALT, AST, and NLR for HBV-HCC was superior to single biomarker or any other combinations among these patients, and its diagnostic equation can be used as useful tool for differentiation of HBV-HCC from CHB.

Dataset Information

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

Publications

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

Similar Datasets

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