Dataset Information

PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role.

ABSTRACT:

Background

Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 (PLCE1) single-nucleotide polymorphisms (SNPs) and GC susceptibility, but its relationship with GC prognosis lacked exploration, and the specific mechanisms were not elaborated fully yet. This study aimed to further explore the possible mechanism of the association between PLCE1 polymorphisms and GC.

Materials and methods

A case-control study, including 588 GC patients and 703 healthy controls among the Chinese Han population, was performed to investigate the association between SNPs of PLCE1 and GC risk by logistic regression in multiple genetic models. The prognostic value of PLCE1 in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of PLCE1, various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations.

Results

Rs3765524 C > T, rs2274223 A > G and rs3781264 T > C in PLCE1 were associated with the increased risk of GC. The overall survival and progression-free survival of patients with high expression of PLCE1 were significantly lower than those with low expression [HR (95% CI) = 1.38 (1.1-1.63), P < 0.01; HR (95% CI) = 1.4 (1.07-1.84), P = 0.01]. Bioinformatic analysis revealed that PLCE1 was associated with protein phosphorylation and played a crucial role in the calcium signal pathway. Two important functional domains, catalytic binding pocket and calcium ion binding pocket, were found by homology modeling of PLCE1 protein; rs3765524 polymorphism could change the efficiency of the former, and rs2274223 polymorphism affected the activity of the latter, which may together play a potentially significant role in the tumorigenesis and prognosis of GC.

Conclusion

Patients with high expression of PLCE1 had a poor prognosis in GC, and SNPs in PLCE1 were associated with GC risk, which might be related to the changes in spatial structure of the protein, especially the variation of the efficiency of PLCE1 in the calcium signal pathway.

SUBMITTER: Hu X

PROVIDER: S-EPMC8438327 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Recent studies have investigated the relationships between PLCE1 polymorphisms and cancer susceptibility. However, some findings lack consistency. Objectives: In the current study, we conducted a meta-analysis to more accurately evaluate the relationships between PLCE1 (rs2274223, rs3765524, rs753724, rs11187842, and rs7922612) single nucleotide polymorphisms (SNPs) and risk for different types of cancer. Methods: We performed a comprehensive search strategy in PubMed, Web of Science, Medline, EMbase, and Scopus for articles available until 19 March 2018. A total of 54 case-control studies comprising 17,955 cases and 20,400 controls were included in the current meta-analysis, which together comprised a total of 32 publications. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the PLCE1 polymorphisms and cancer susceptibility. All statistical analyses were performed using Stata 11 software. Results: Results of the meta-analysis demonstrated that the rs2274223 polymorphism showed a significant correlation with increased overall cancer susceptibility (AG vs. AA: OR 1.168, 95% CI 1.084-1.259; GG vs. AA: OR 1.351, 95% CI 1.163-1.570; AG+GG vs. AA: OR 1.193, 95% CI 1.103-1.290; GG vs. AA+AG: OR 1.262, 95% CI 1.102-1.446; G vs. A: OR 1.163, 95% CI 1.089-1.242). Results of subgroup analysis showed that the rs2274223 polymorphism was associated with higher risk for esophageal cancer and gastric cancer relative to colorectal cancer and head and neck cancer. In addition, the rs2274223 polymorphism was found to be associated with increased cancer risk, especially among the subgroups comprising Asians, studies with population-based controls, studies employing the TaqMan genotyping method, and studies consistent with Hardy-Weinberg equilibrium (HWE). The association between the rs3765524 polymorphism and reduced overall cancer risk was detected in one specific genetic model (CT vs. CC: OR 0.681, 95% CI 0.523-0.886). Results of subgroup analysis showed that the rs3765524 polymorphism was associated with cancer risk in a specific genetic model among the subgroups of colorectal cancer, esophageal cancer, Asians, studies with population-based controls, and studies consistent with HWE. However, relationships among the PLCE1 rs753724, rs11187842, and rs7922612 polymorphisms and tumor risk were not identified. Conclusions: Results of the current meta-analysis suggested that PLCE1 (rs2274223, rs3765524) polymorphisms are associated with cancer susceptibility.