LARS2 DNA methylation predicts the prognosis in colon cancer

Abstract Colon cancer is a highly aggressive solid tumor. Because most studies have focused on the intrinsic oncogenic pathways of tumors, we focused on the relationship between DNA methylation genes in the tumor immune microenvironment and colon cancer prognosis. We download RNA-seq data from the T...

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Main Authors: Yingzhou Fu, Wei Xie, Qifan Ren, Jiao Wu, Ying Long, Ying Liu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10669-9
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author Yingzhou Fu
Wei Xie
Qifan Ren
Jiao Wu
Ying Long
Ying Liu
author_facet Yingzhou Fu
Wei Xie
Qifan Ren
Jiao Wu
Ying Long
Ying Liu
author_sort Yingzhou Fu
collection DOAJ
description Abstract Colon cancer is a highly aggressive solid tumor. Because most studies have focused on the intrinsic oncogenic pathways of tumors, we focused on the relationship between DNA methylation genes in the tumor immune microenvironment and colon cancer prognosis. We download RNA-seq data from the TCGA dataset. DNA methylation genes were scored using the GSVA method, and this score was subjected to GSEA, GO and KEGG enrichment analysis. Then, in vitro experiments examined the effect of silencing LARS2 on the proliferation and apoptosis of HCT116 cells. We obtained 2635 genes, 144 were obtained after single factor screening, and 8 genes were obtained through random forest dimensionality reduction. They are LARS2, TEX2, BRIP1, QSOX2, HOOK1, COX19, NEK4 and STXBP4. Survival analysis indicated that patients with high Riskscore had poor prognosis. There were significant differences in the expression of DNA methylation genes between the two groups with high and low Riskscore. The immune checkpoints of different Riskscore groups include Antigen present, Ligand, Receptor, Co-inhibitor, Co-stimulator, Other, and Cell adhesion. There were significant differences in the expression of genes and DNA integrity checkpoint, histone deacetylation, mitotic DNA damage checkpoint, TGF-beta signaling pathway, Platinum drug resistance and Protein processing in endoplasmic reticlum pathway at the level of Antigen present. Silencing of LARS2 decreased the proliferative capacity and increased the apoptosis rate of HCT116. Our findings suggest that LARS2 methylation could affects colon cancer development.
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institution Kabale University
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spelling doaj-art-657eb8cf4f8c4035af8577dc28d5f65a2025-08-20T04:02:45ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-10669-9LARS2 DNA methylation predicts the prognosis in colon cancerYingzhou Fu0Wei Xie1Qifan Ren2Jiao Wu3Ying Long4Ying Liu5Hunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityThe First Affiliated Hospital, Hengyang Medical School, University of South ChinaHunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityHunan Provincial Clinical Research Centre for Oncoplastic Surgery, Hunan Cancer Hospital / The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South UniversityAbstract Colon cancer is a highly aggressive solid tumor. Because most studies have focused on the intrinsic oncogenic pathways of tumors, we focused on the relationship between DNA methylation genes in the tumor immune microenvironment and colon cancer prognosis. We download RNA-seq data from the TCGA dataset. DNA methylation genes were scored using the GSVA method, and this score was subjected to GSEA, GO and KEGG enrichment analysis. Then, in vitro experiments examined the effect of silencing LARS2 on the proliferation and apoptosis of HCT116 cells. We obtained 2635 genes, 144 were obtained after single factor screening, and 8 genes were obtained through random forest dimensionality reduction. They are LARS2, TEX2, BRIP1, QSOX2, HOOK1, COX19, NEK4 and STXBP4. Survival analysis indicated that patients with high Riskscore had poor prognosis. There were significant differences in the expression of DNA methylation genes between the two groups with high and low Riskscore. The immune checkpoints of different Riskscore groups include Antigen present, Ligand, Receptor, Co-inhibitor, Co-stimulator, Other, and Cell adhesion. There were significant differences in the expression of genes and DNA integrity checkpoint, histone deacetylation, mitotic DNA damage checkpoint, TGF-beta signaling pathway, Platinum drug resistance and Protein processing in endoplasmic reticlum pathway at the level of Antigen present. Silencing of LARS2 decreased the proliferative capacity and increased the apoptosis rate of HCT116. Our findings suggest that LARS2 methylation could affects colon cancer development.https://doi.org/10.1038/s41598-025-10669-9Colon cancerDNA methylationRiskscoreImmune infiltration
spellingShingle Yingzhou Fu
Wei Xie
Qifan Ren
Jiao Wu
Ying Long
Ying Liu
LARS2 DNA methylation predicts the prognosis in colon cancer
Scientific Reports
Colon cancer
DNA methylation
Riskscore
Immune infiltration
title LARS2 DNA methylation predicts the prognosis in colon cancer
title_full LARS2 DNA methylation predicts the prognosis in colon cancer
title_fullStr LARS2 DNA methylation predicts the prognosis in colon cancer
title_full_unstemmed LARS2 DNA methylation predicts the prognosis in colon cancer
title_short LARS2 DNA methylation predicts the prognosis in colon cancer
title_sort lars2 dna methylation predicts the prognosis in colon cancer
topic Colon cancer
DNA methylation
Riskscore
Immune infiltration
url https://doi.org/10.1038/s41598-025-10669-9
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AT qifanren lars2dnamethylationpredictstheprognosisincoloncancer
AT jiaowu lars2dnamethylationpredictstheprognosisincoloncancer
AT yinglong lars2dnamethylationpredictstheprognosisincoloncancer
AT yingliu lars2dnamethylationpredictstheprognosisincoloncancer