PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role
BackgroundGastric 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 s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.714915/full |
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| author | Xi’e Hu Jintong Jia Zhenyu Yang Songhao Chen Jingyi Xue Sensen Duan Ping Yang Shujia Peng Lin Yang Lijuan Yuan Guoqiang Bao |
| author_facet | Xi’e Hu Jintong Jia Zhenyu Yang Songhao Chen Jingyi Xue Sensen Duan Ping Yang Shujia Peng Lin Yang Lijuan Yuan Guoqiang Bao |
| author_sort | Xi’e Hu |
| collection | DOAJ |
| description | BackgroundGastric 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 MethodsA 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.ResultsRs3765524 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.ConclusionPatients 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. |
| first_indexed | 2024-12-17T22:45:12Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-17T22:45:12Z |
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| series | Frontiers in Genetics |
| spelling | doaj.art-26be6915fe5f47dabd65bf772465c8052022-12-21T21:29:49ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-08-011210.3389/fgene.2021.714915714915PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential RoleXi’e Hu0Jintong Jia1Zhenyu Yang2Songhao Chen3Jingyi Xue4Sensen Duan5Ping Yang6Shujia Peng7Lin Yang8Lijuan Yuan9Guoqiang Bao10Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaSingleron Biotechnologies, Nanjing, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaThe Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, ChinaBackgroundGastric 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 MethodsA 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.ResultsRs3765524 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.ConclusionPatients 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.714915/fullgastric cancerPLCE1polymorphismriskprognosisbioinformatics |
| spellingShingle | Xi’e Hu Jintong Jia Zhenyu Yang Songhao Chen Jingyi Xue Sensen Duan Ping Yang Shujia Peng Lin Yang Lijuan Yuan Guoqiang Bao PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role Frontiers in Genetics gastric cancer PLCE1 polymorphism risk prognosis bioinformatics |
| title | PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role |
| title_full | PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role |
| title_fullStr | PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role |
| title_full_unstemmed | PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role |
| title_short | PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role |
| title_sort | plce1 polymorphisms are associated with gastric cancer risk the changes in protein spatial structure may play a potential role |
| topic | gastric cancer PLCE1 polymorphism risk prognosis bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.714915/full |
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