AUTHOR=Hu Xi’e , Jia Jintong , Yang Zhenyu , Chen Songhao , Xue Jingyi , Duan Sensen , Yang Ping , Peng Shujia , Yang Lin , Yuan Lijuan , Bao Guoqiang 

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

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.714915

DOI=10.3389/fgene.2021.714915

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 (<italic>PLCE1</italic>) 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 <italic>PLCE1</italic> polymorphisms and GC.</p></sec><sec><title>Materials and Methods</title><p>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 <italic>PLCE1</italic> and GC risk by logistic regression in multiple genetic models. The prognostic value of <italic>PLCE1</italic> in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of <italic>PLCE1</italic>, various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations.</p></sec><sec><title>Results</title><p>Rs3765524 C &gt; T, rs2274223 A &gt; G and rs3781264 T &gt; C in <italic>PLCE1</italic> 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), <italic>P</italic> &lt; 0.01; HR (95% CI) = 1.4 (1.07–1.84), <italic>P</italic> = 0.01]. Bioinformatic analysis revealed that <italic>PLCE1</italic> 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.</p></sec><sec><title>Conclusion</title><p>Patients with high expression of <italic>PLCE1</italic> had a poor prognosis in GC, and SNPs in <italic>PLCE1</italic> 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.</p></sec>