Dataset Information

Tumor microenvironment characteristics and prognostic role of m⁶A modification in lung squamous cell carcinoma.

ABSTRACT:

Background

It has recently been determined that N6-methyladenosine (m⁶A) RNA methylation regulators have prominent effects on several cancers. However, the potential role of m⁶A modification in lung squamous cell carcinoma (LUSC) remains unclear.

Methods

We evaluated the modification pattern of m⁶A and studied the biological function of m⁶A regulators in LUSC. Then, we constructed the m6Ascore to predict the prognosis of LUSC and analyzed the relationship between the m6Ascore and tumor mutation burden, immune cell infiltration, and immunotherapy.

Result

In the unsupervised consensus cluster analysis, three different m6Aclusters were identified, which correspond to an immune activation state, a moderate immune activation state, and an immune tolerance state. Forty-two genes related to the m⁶A phenotype were used to construct the m6Ascore; subsequently, multiple validations of the m6Ascore were carried out to determine the relationship between the score and immune cell infiltration and response to CTLA-4/PD-1 inhibitor treatment. Further analysis revealed that the m6Ascore could effectively predict the prognosis of LUSC and that the m⁶A phenotype-related genes, FAM162A and LOM4, might be potential biomarkers.

Conclusion

These findings highlight the potential role of m⁶A modification in the prognosis, TME, and immunotherapy of LUSC and have profound implications for developing more effective personalized treatment strategies for LUSC.

SUBMITTER: Li P

PROVIDER: S-EPMC10918158 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Tumor microenvironment characteristics and prognostic role of m<sup>6</sup>A modification in lung squamous cell carcinoma.

Li Pei P Xiong Peiyu P Li Xinyun X Zhang Xiaobo X Chen Xu X Zhang Wei W Jia Bo B Lai Yu Y

Heliyon 20240228 5

<h4>Background</h4>It has recently been determined that N6-methyladenosine (m<sup>6</sup>A) RNA methylation regulators have prominent effects on several cancers. However, the potential role of m<sup>6</sup>A modification in lung squamous cell carcinoma (LUSC) remains unclear.<h4>Methods</h4>We evaluated the modification pattern of m<sup>6</sup>A and studied the biological function of m<sup>6</sup>A regulators in LUSC. Then, we constructed the m6Ascore to predict the prognosis of LUSC and analyze ...[more]

PMID: 38455573

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Project description:BackgroundThe incidence rate of lung adenocarcinoma (LUAD) is rapidly increasing. Recent studies have reported that histone acetylation modification plays an important role in the occurrence and development of tumors. However, the potential role of modification of histone acetylation modification in the development of tumor immune microenvironment is still unclear.MethodsIn this study, we comprehensively evaluated the acetylation modification patterns of LUAD samples obtained from various different databases based on 36 histone modification regulators, and constructed a prognostic model based on The Cancer Genome Atlas (TCGA) LUAD cohort using the Cox regression method. The close relationship between histone acetylation and tumor immune characteristics was further studied, including immune infiltration, immune escape and immunotherapy. Finally, we combined three cohort (GSE30219, GSE72094 and GSE50081) from Gene Expression Omnibus (GEO) database to verify the above results.ResultsWe analyzed the expression, mutation and interaction of 36 histone acetylation regulated genes. After Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO), 5 genes (KAT2B, SIRT2, HDAC5, KAT8, HDAC2) were screened to establish the prognosis model and calculate the risk score. Then, patients in the TCGA cohort were divided into high- and low-risk groups based on the risk scores. Further analysis indicated that patients in the high-risk group exhibited significantly reduced overall survival (OS) compared with those in the low-risk group. The high- and low-risk groups exhibited significant differences in terms of tumor immune characteristics, such as immune infiltration, immune escape and immunotherapy. The high-risk group had lower immune score, less immune cell infiltration and higher clinical stage. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. In addition, drugs sensitive for this classification were identified. Finally, the efficacy of the prognostic model was validated by cohort (GSE30219, GSE72094 and GSE50081) from GEO database.ConclusionsOur study provided a robust signature for predicting changing prognosis of patients with LUAD. Thus, it appears to be a potentially useful prognostic tool. Moreover, the important relationship between histone acetylation and tumor immune microenvironment was revealed.

Project description:Non-small-cell lung cancers (NSCLCs) are largely classified into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), which have different therapeutic options according to its molecular profiles and immune checkpoint expression, especially PD-L1, which is a suppressive factor in the tumor microenvironment. The tumor microenvironment can be altered by the genomic mutations on specific innate immune genes as well as tumor suppressor genes, so it is essential to comprehend the association between tumor microenvironment and tumor suppressor genes to discover the promising immunotherapeutic strategy to overcome the resistance of immune check point blockade. In this study, we aimed to analyze how the somatic mutations in tumor suppressor genes affect the tumor immune microenvironment through a comprehensive analysis of mutational profiling on the representative tumor suppressor genes (TP53, CDKN2A, PTEN, RB1, BRCA1, BRCA2) and immune gene expression in The Cancer Genome Atlas (TCGA) 155 lung squamous cell carcinoma (LUSC) and 196 lung adenocarcinoma (LUAD) samples. Several microenvironmental factors, such as the infiltrating immune and stromal cells, were suppressed by the mutated tumor suppressor genes in LUSC, unlike in the LUAD samples. In particular, infiltrating immune cells such as macrophage, neutrophil, and dendritic cells were significantly reduced in tumors with mutated tumor suppressor genes' group. In addition, the gene expressions for interleukin production and lymphocyte differentiation and PGC, C7, HGF, PLA2G2A, IL1RL1, CCR2, ALOX15B, CXCL11, FCN3 were significantly down-regulated, which were key immune genes for the cross-talk between LUSC microenvironment and tumor suppressors. Therefore, we generated evidence that TSG mutations in LUSC have an impact on tumor immune microenvironment, which suggests that TSG non-mutated patients will have the more inflamed tumors and are more likely to respond to immune checkpoint blockade therapy.

Dataset Information

Tumor microenvironment characteristics and prognostic role of m⁶A modification in lung squamous cell carcinoma.

Background

Methods

Result

Conclusion

Publications

Tumor microenvironment characteristics and prognostic role of m<sup>6</sup>A modification in lung squamous cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Tumor microenvironment characteristics and prognostic role of m6A modification in lung squamous cell carcinoma.

Background

Methods

Result

Conclusion

Publications

Tumor microenvironment characteristics and prognostic role of m<sup>6</sup>A modification in lung squamous cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Tumor microenvironment characteristics and prognostic role of m⁶A modification in lung squamous cell carcinoma.