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The diagnostic and prognostic value of CHFR hypermethylation in colorectal cancer, a meta-analysis and literature review.

ABSTRACT: The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This study aimed to conduct a meta-analysis and literature review and investigate clinicopathological significance of CHFR promoter hypermethylation in CRC. The following online database were used: PubMed, EMBASE, and Web of Science up to March 2017. Odds Ratios (OR) and Hazard Ratios (HR) with 95% corresponding confidence intervals (CIs) were calculated. A total of seven relevant articles were available for meta-analysis which included 966 patients. The frequency of CHFR promoter hypermethylation significantly increased in CRC compared to normal colorectal mucosa tissue, pooled OR was 8.35, p < 0.00001. CHFR promoter hypermethylation was not significantly correlated to stage, OR was 1.16, p = 0.63. However, CHFR promoter hypermethylation was more frequently observed in CRC with positive lymph nodes metastasis than CRC with negative lymph nodes metastasis, OR was 0.46, p = 0.03. Additionally CHFR promoter hypermethylation was significantly related to poor overall survival in patients with CRC, HR was 0.62, p = 0.008. Based on these results, tumor CHFR promoter hypermethylation is not only a diagnostic biomarker for CRC, but also a prognostic marker. CHFR promoter hypermethylation is significantly associated with worse overall survival in patients with CRC. Our data suggested that CHFR could be a potential drug target for development of demethylation treatment for patients with CRC.

SUBMITTER: Sun Z

PROVIDER: S-EPMC5687676 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The diagnostic and prognostic value of CHFR hypermethylation in colorectal cancer, a meta-analysis and literature review.

Sun Zhulei Z Liu Juncai J Jing Hong H Dong Shu-Xiao SX Wu Jiang J

Oncotarget 20170720 51

The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This study aimed to conduct a meta-analysis and literature review and investigate clinicopathological significance of CHFR promoter hypermethylation in CRC. The followi ...[more]

PMID: 29179506

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Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.

Project description:The application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive.The aim of this study was to systematically evaluate this issue.An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies.For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan-Meier curves.Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46-0.88), 0.74 (95% CI: 0.56-0.86), and 0.79 (95% CI: 0.75-0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR?=?1.76, 95% CI: 1.42-2.19, P?<?0.001) and disease-free survival (DFS) (pooled HR?=?2.97, 95% CI: 1.76-5.01, P?<?0.001). The synthesized Kaplan-Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P?=?0.0027) and DFS (P?<?0.001), which further support the prognostic value of serum IL-6 in CRC patients.The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival. The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485).

Dataset Information

The diagnostic and prognostic value of CHFR hypermethylation in colorectal cancer, a meta-analysis and literature review.

Publications

The diagnostic and prognostic value of <i>CHFR</i> hypermethylation in colorectal cancer, a meta-analysis and literature review.

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