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. 2017 Dec 26;9(17):13222-13230.
doi: 10.18632/oncotarget.23812. eCollection 2018 Mar 2.

The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with hepatocellular carcinoma

Xiao Zhu  1   2   3 , Qingming Kong  4 , Liwei Xie  5 , Zhihong Chen  1 , Hongmei Li  1 , Zhu Zhu  1 , Yongmei Huang  1   6 , Feifei Lan  7 , Haiqing Luo  1   8 , Jingting Zhan  1   6 , Hongrong Ding  1 , Jinli Lei  1   6 , Qin Xiao  9 , Weiming Fu  10 , Wenguo Fan  11 , Jinfang Zhang  12 , Hui Luo  1   6
Affiliations

The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with hepatocellular carcinoma

Xiao Zhu et al. Oncotarget. .

Abstract

Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and CHD5 mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and CHD5 mRNA expressions.

Keywords: chromodomain-helicase-DNA-binding protein 5; hepatocellular carcinoma; linkage disequilibrium; prognosis; single-nucleotide polymorphisms.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Kaplan-Meier survival curves according to haplotypes (block 3) in the discovery, replication and combined studies
P value was calculated using a log-rank test.
Figure 2
Figure 2. CHD5 structure, mutations and expressions in silico
(A) CHD5 in chromosome 1p36.31 and its transcriptional direction from the National Center for Biotechnology Information (NCBI, https://www.ncbi.nlm.nih.gov/). (B) CHD5 gene mutations from TCGA (https://cancergenome.nih.gov/). The Cancer Genome Atlas (TCGA) hepatocellular carcinoma datasets and the related clinicopathologic information of the included patients were obtained from the cBioPortal (http://www.cbioportal.org/) for Cancer Genomics generated by Memorial Sloan-Kettering Cancer Center. (C) CHD5 gene ECR generated from the UCSC Genome Browser (https://genome.ucsc.edu/). (D) the deletions of CHD5 from TCGA in silico analysis. (E) copy-number alterations from GISTIC (https://software.broadinstitute.org/software/cprg/?q = node/31). By separating somatic copy-number alterations (SCNAs) profiles into underlying arm-level and focal alterations, GISTIC estimates the background rates for each category as well as defines the boundaries of SCNA regions. (F) CHD5 expressions in HCC samples and matched normal samples comparing of average beta value from TCGA.
Figure 3
Figure 3. Correlation between CHD5 mRNA expressions and haplotypes (block 3) from EBV-transformed B lymphoblastoid cell lines from different populations available by SNPexp
See this image and copyright information in PMC

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