Relationships between p14ARF Gene Methylation and Clinicopathological Features of Colorectal Cancer: A Meta-Analysis.

Hao Zhang,Yongchun Song,Jianguo Lai,Chengxue Dang,Dongmei Diao,Bing-Hua Jiang,Wenhan Li,Zhangjian Zhou

doi:10.1371/journal.pone.0152050

Hao Zhang, Yongchun Song + Show 6 more

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https://doi.org/10.1371/journal.pone.0152050

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Abstract

We conducted a meta-analysis to explore the relationships between p14ARF gene methylation and clinicopathological features of colorectal cancer (CRC). Databases, including Pubmed, Embase and Cochrane Library, were searched and, finally, a total of 18 eligible researches encompassing 1988 CRC patients were selected. Combined odds ratios (ORs) with 95% confidence intervals (95% CIs) were evaluated under a fixed effects model for absence of heterogeneity. Significant associations were observed between p14ARF gene methylation and tumor location (OR = 2.35, 95% CI: 1.55–3.55, P = 0.001), microsatellite instability (MSI) status (OR = 3.28, 95% CI: 2.12–5.07, P<0.0001). However, there were no significant associations between p14ARF gene methylation and tumor stage, tumor differentiation. We concluded that p14ARF gene methylation may be significantly associated with tumor location, and MSI status of CRC.

Highlights

We used a set of inclusion criteria: (1) Histopathologic information of colorectal cancer (CRC) patients were confirmed by the pathologist review; (2) Methylation analysis of p14ARF gene was performed in primary tumor tissues after operation, not in normal colonic mucosa, serum, and peripheral blood leukocyte of CRC patients; (3) Data with regard to the relationships between p14ARF gene methylation and clinicopathological features of CRC patients was provided, which is conducive to estimating the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs); (4) The latest or most comprehensive data was our choice when duplications were published
As for the CRC tumor location, our results revealed that the classification of proximal vs. distal was significantly correlated with p14ARF gene methylation (OR = 2.35, 95% CI: 1.55–3.55, p = 0.001) (Fig 2D)
We explored whether p14ARF gene methylation was associated with some clinicopathological features of CRC patients through 18 included studies

Summary

Introduction

Data Availability Statement: All relevant data are within the paper and its Supporting Information files. As one of the most important epigenetic changes, DNA methylation has been noted in the carcinogenesis of many human cancers, including CRC [4,5,6,7,8]. The alterations of P53/MDM2/p14ARF pathway always occur during CRC progression. P14ARF Gene Methylation and Colorectal Cancer and protein expression [12,13,14]. The relationships between p14ARF gene methylation and clinicopathological features of CRC remain controversial. Epigenetic markers such as p14ARF gene methylation may be used to more accurately classify subgroups of CRC patients. We conducted a meta-analysis to quantify the associations between p14ARF gene methylation and clinicopathological features of CRC

Materials and Methods

Results

Discussion