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M⁶A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration.

ABSTRACT: The correlation of m⁶A-related lncRNAs with the prognosis and immune microenvironment of cervical cancer is not yet clear. In this study, we identified 7 m⁶A-related prognostic lncRNAs by Pearson correlation and univariate Cox regression analyses based on TCGA-cervical cancer dataset. Then, patients were divided into two clusters by consensus clustering based on the 7 m⁶A-related prognostic lncRNA expression. Cluster 1 was characterized by survival and stage disadvantage, enrichment of immunosuppressive and carcinogenic activation pathways. Besides, cluster 1 had higher immunosuppressive factor TGFbeta and lower immune cell infiltration compared with cluster 2. According to the expression of 7 m⁶A-related lncRNA, a 6-m⁶A-related lncRNA risk score model was established in the training set by LASSO regression analysis. The high-risk group had worse overall survival than the low-risk group. No matter in the training or validation sets, the m⁶A-related lncRNA risk score was an independent prognostic factor for overall survival. Meanwhile, we validated the independent prognostic value of risk score in the disease-specific survival and progression-free survival by multivariate Cox analysis. The high-risk group was characterized by higher TGFbeta and regulatory T cell and was rich in malignant pathways. Additionally, we also detected and compared the expression levels of four m⁶A-related prognostic lncRNA in 9 tumor samples and 9 normal tissues using quantitative real-time polymerase chain reaction assay. In conclusion, the novel m⁶A-related lncRNA risk score is a potential prognostic predictor of cervical cancer patients. These 6 m⁶A-related lncRNAs might serve as key mediators of the immune microenvironment and represent promising therapeutic targets for improving cervical cancer prognosis.

SUBMITTER: Jia H

PROVIDER: S-EPMC9011170 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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m6A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration.

Jia Haixia H Hao Suhua S Cao Meiting M Wang Lifang L Bai Hua H Shui Wen W Yang Xiaotang X

Disease markers 20220411

The correlation of m6A-related lncRNAs with the prognosis and immune microenvironment of cervical cancer is not yet clear. In this study, we identified 7 m6A-related prognostic lncRNAs by Pearson correlation and univariate Cox regression analyses based on TCGA-cervical cancer dataset. Then, patients were divided into two clusters by consensus clustering based on the 7 m6A-related prognostic lncRNA expression. Cluster 1 was characterized by survival and stage disa ...[more]

PMID: 35432630

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Project description:BackgroundSeveral recent studies have confirmed epigenetic regulation of the immune response. However, the potential role of RNA N6-methyladenosine (m6A) modifications in cervical cancer and tumour microenvironment (TME) cell infiltration remain unclear.ResultsWe evaluated and analysed m6A modification patterns in 307 cervical cancer samples from The Cancer Genome Atlas (TCGA) dataset based on 13 m6A regulators. Pearson correlation analysis was used to identify lncRNAs associated with m6A, followed by univariate Cox regression analysis to screen their prognostic role in cervical cancer patients. We also correlated TME cell infiltration characteristics with modification patterns. We screened six m6A-associated lncRNAs as prognostic lncRNAs and established the prognostic profile of m6A-associated lncRNAs by least absolute shrinkage and choice of operator (LASSO) Cox regression. The corresponding risk scores of the patients were derived based on their prognostic features, and the correlation between this feature model and disease prognosis was analysed. The prognostic model constructed based on the TCGA-CESC (The Cancer Genome Cervical squamous cell carcinoma and endocervical adenocarcinoma) dataset showed strong prognostic power in the stratified analysis and was confirmed as an independent prognostic indicator for predicting the overall survival of patients with CESC. Enrichment analysis showed that biological processes, pathways, and markers associated with malignancy were more common in the high-risk subgroup. Risk scores were strongly correlated with the tumour grade. ECM receptor interactions and pathways in cancer were enriched in Cluster 2, while oxidative phosphorylation and other biological processes were enriched in Cluster 1. The expression of immune checkpoint molecules, including programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), was significantly increased in the high-risk subgroup, suggesting that this prognostic model could be a predictor of immunotherapy.ConclusionsThis study reveals that m6A modifications play an integral role in the diversity and complexity of TME formation. Assessing the m6A modification patterns of individual tumours will help improve our understanding of TME infiltration characteristics and thus guide immunotherapy more effectively. We also developed an independent prognostic model based on m6A-associated lncRNAs as a predictor of overall survival, which can also be used as a predictor of immunotherapy.

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M⁶A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration.

Publications

m<sup>6</sup>A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration.

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Dataset Information

M6A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration.

Publications

m<sup>6</sup>A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M⁶A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration.