Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma

Chen, Junxing; Liu, Weinan; Du, Jiabin; Wang, Pengcheng; Wang, Jintian; Yang, Kai

doi:10.3389/fgene.2021.778095

Cited by 3 publications

(2 citation statements)

References 41 publications

(39 reference statements)

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“…Our study demonstrated that the mutation rate of the TTN gene was the highest in high-risk patients, albeit lower than that observed in low-risk patients. A previous investigation has corroborated the association between increased gastric cancer aggressiveness and a reduced frequency of TTN mutations [34]. This nding further elucidates the poorer prognosis observed in the high-risk group from the perspective of TMB.…”

Section: Discussionsupporting

confidence: 76%

A novel endoplasmic reticulum stress-related lncRNA signature for prognosis prediction and immune response evaluation in Stomach adenocarcinoma

Song

et al. 2023

Preprint

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Background: Stomach adenocarcinoma (STAD) is a significant contributor to cancer-related mortality worldwide. Although previous research has identified endoplasmic reticulum stress (ERS) as a regulator of various tumor-promoting properties of cancer cells, the impact of ERS-related long non-coding RNAs (lncRNAs) on STAD prognosis has not yet been investigated. Therefore, our study aims to develop and validate an ERS-related lncRNA signature that can accurately predict the prognosis of STAD patients. Methods: We collected RNA expression profiles and clinical data of STAD patients from The Cancer Genome Atlas (TCGA) and identified ERS-related genes from the Molecular Signature Database (MSigDB). Co-expression analysis enabled us to identify ERS-related lncRNAs, and we applied univariate Cox, least absolute shrinkage, and selection operator (LASSO), and multivariate Cox regression analyses to construct a predictive signature comprising of 9 ERS-related lncRNAs. We assessed the prognostic accuracy of our signature using Kaplan-Meier survival analysis and performed tumor mutational burden (TMB) and tumor immune microenvironment (TIME) analyses. Enrichment analysis was used to investigate the functions and biological processes of the signature, and we identified two distinct STAD patient subgroups through consensus clustering. Finally, we performed drug sensitivity analysis and immunologic efficacy analysis to explore further insights. Results: The 9 ERS related-lncRNAs signature demonstrated satisfactory predictive performance as an independent prognostic marker and was significantly associated with STAD clinicopathological characteristics. Furthermore, patients in the high-risk group displayed a worse STAD prognosis than those in the low-risk group. Notably, gene set enrichment analysis (GSEA) revealed significant enrichment of extracellular matrix pathways in the high-risk group, indicating their involvement in STAD progression. Additionally, the high-risk group exhibited significantly lower TMB expression levels than the low-risk group. Consensus clustering revealed two distinct STAD patient subgroups, with Cluster 1 exhibiting higher immune cell infiltration and more active immune functions. Drug sensitivity analysis suggested that the low-risk group was more responsive to oxaliplatin, epirubicinl, and other drugs. Conclusion: Our study highlights the crucial regulatory roles of ERS-related lncRNAs in STAD, with significant clinical implications. The 9-lncRNA signature we have constructed represents a reliable prognostic indicator that has the potential to inform more personalized treatment decisions for STAD patients. These findings shed new light on the pathogenesis of STAD and its underlying molecular mechanisms, offering opportunities for novel therapeutic strategies to be developed for STAD patients.

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Section: Discussionsupporting

confidence: 76%

A novel endoplasmic reticulum stress-related lncRNA signature for prognosis prediction and immune response evaluation in Stomach adenocarcinoma

Song

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Our study demonstrated that the mutation rate of the TTN gene was the highest in high-risk patients, albeit lower than that observed in low-risk patients. A previous investigation has corroborated the association between increased gastric cancer aggressiveness and a reduced frequency of TTN mutations [ 60 ]. This finding further elucidates the poorer prognosis observed in the high-risk group from the perspective of TMB.…”

Section: Discussionmentioning

confidence: 62%

A novel endoplasmic reticulum stress-related lncRNA signature for prognosis prediction and immune response evaluation in Stomach adenocarcinoma

Song,

Su,

et al. 2023

BMC Gastroenterol

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background Stomach adenocarcinoma (STAD) is a significant contributor to cancer-related mortality worldwide. Although previous research has identified endoplasmic reticulum stress (ERS) as a regulator of various tumor-promoting properties of cancer cells, the impact of ERS-related long non-coding RNAs (lncRNAs) on STAD prognosis has not yet been investigated. Therefore, our study aims to develop and validate an ERS-related lncRNA signature that can accurately predict the prognosis of STAD patients. Methods We collected RNA expression profiles and clinical data of STAD patients from The Cancer Genome Atlas (TCGA) and identified ERS-related genes from the Molecular Signature Database (MSigDB). Co-expression analysis enabled us to identify ERS-related lncRNAs, and we applied univariate Cox, least absolute shrinkage, and selection operator (LASSO), and multivariate Cox regression analyses to construct a predictive signature comprising of 9 ERS-related lncRNAs. We assessed the prognostic accuracy of our signature using Kaplan-Meier survival analysis, and validated our predictive signature in an independent gene expression omnibus (GEO) cohort. We also performed tumor mutational burden (TMB) and tumor immune microenvironment (TIME) analyses. Enrichment analysis was used to investigate the functions and biological processes of the signature, and we identified two distinct STAD patient subgroups through consensus clustering. Finally, we performed drug sensitivity analysis and immunologic efficacy analysis to explore further insights. Results The 9 ERS related-lncRNAs signature demonstrated satisfactory predictive performance as an independent prognostic marker and was significantly associated with STAD clinicopathological characteristics. Furthermore, patients in the high-risk group displayed a worse STAD prognosis than those in the low-risk group. Notably, gene set enrichment analysis (GSEA) revealed significant enrichment of extracellular matrix pathways in the high-risk group, indicating their involvement in STAD progression. Additionally, the high-risk group exhibited significantly lower TMB expression levels than the low-risk group. Consensus clustering revealed two distinct STAD patient subgroups, with Cluster 1 exhibiting higher immune cell infiltration and more active immune functions. Drug sensitivity analysis suggested that the low-risk group was more responsive to oxaliplatin, epirubicinl, and other drugs. Conclusion Our study highlights the crucial regulatory roles of ERS-related lncRNAs in STAD, with significant clinical implications. The 9-lncRNA signature we have constructed represents a reliable prognostic indicator that has the potential to inform more personalized treatment decisions for STAD patients. These findings shed new light on the pathogenesis of STAD and its underlying molecular mechanisms, offering opportunities for novel therapeutic strategies to be developed for STAD patients.

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Multiomics Integration at Single-Cell Resolution Using Bayesian Networks: A Case Study in Hepatocellular Carcinoma

Jihad

Yet

2023

OMICS: A Journal of Integrative Biology

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Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma

Cited by 3 publications

References 41 publications

A novel endoplasmic reticulum stress-related lncRNA signature for prognosis prediction and immune response evaluation in Stomach adenocarcinoma

A novel endoplasmic reticulum stress-related lncRNA signature for prognosis prediction and immune response evaluation in Stomach adenocarcinoma

A novel endoplasmic reticulum stress-related lncRNA signature for prognosis prediction and immune response evaluation in Stomach adenocarcinoma

Multiomics Integration at Single-Cell Resolution Using Bayesian Networks: A Case Study in Hepatocellular Carcinoma

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