Dataset Information

Identification and Characterization of Immunogene-Related Alternative Splicing Patterns and Tumor Microenvironment Infiltration Patterns in Breast Cancer.

ABSTRACT: Alternative splicing (AS) plays a crucial role in tumor development and tumor microenvironment (TME) formation. However, our current knowledge about AS, especially immunogene-related alternative splicing (IGAS) patterns in cancers, remains limited. Herein, we identified and characterized post-transcriptional mechanisms of breast cancer based on IGAS, TME, prognosis, and immuno/chemotherapy. We screened the differentially spliced IGAS events and constructed the IGAS prognostic model (p-values < 0.001, AUC = 0.939), which could be used as an independent prognostic factor. Besides, the AS regulatory network suggested a complex cooperative or competitive relationship between splicing factors and IGAS events, which explained the diversity of splice isoforms. In addition, more than half of the immune cells displayed varying degrees of infiltration in the IGAS risk groups, and the prognostic characteristics of IGAS demonstrated a remarkable and consistent trend correlation with the infiltration levels of immune cell types. The IGAS risk groups showed substantial differences in the sensitivity of immunotherapy and chemotherapy. Finally, IGAS clusters defined by unsupervised cluster analysis had distinct prognostic patterns, suggesting an essential heterogeneity of IGAS events. Significant differences in immune infiltration and unique prognostic capacity of immune cells were also detected in each IGAS cluster. In conclusion, our comprehensive analysis remarkably enhanced the understanding of IGAS patterns and TME in breast cancer, which may help clarify the underlying mechanisms of IGAS in neoplasia and provide clues to molecular mechanisms of oncogenesis and progression.

SUBMITTER: Guo S

PROVIDER: S-EPMC8833331 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Identification and Characterization of Immunogene-Related Alternative Splicing Patterns and Tumor Microenvironment Infiltration Patterns in Breast Cancer.

Guo Shuang S Wang Xinyue X Zhou Hanxiao H Gao Yue Y Wang Peng P Zhi Hui H Sun Yue Y Hao Yangyang Y Gan Jing J Zhang Yakun Y Sun Jie J Zheng Wen W Zhao Xiaoxi X Xiao Yun Y Ning Shangwei S

Cancers 20220125 3

Alternative splicing (AS) plays a crucial role in tumor development and tumor microenvironment (TME) formation. However, our current knowledge about AS, especially immunogene-related alternative splicing (IGAS) patterns in cancers, remains limited. Herein, we identified and characterized post-transcriptional mechanisms of breast cancer based on IGAS, TME, prognosis, and immuno/chemotherapy. We screened the differentially spliced IGAS events and constructed the IGAS prognostic model (<i>p</i>-val ...[more]

PMID: 35158863

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Project description:N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan-Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to anti-PD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity.

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Dataset Information

Identification and Characterization of Immunogene-Related Alternative Splicing Patterns and Tumor Microenvironment Infiltration Patterns in Breast Cancer.

Publications

Identification and Characterization of Immunogene-Related Alternative Splicing Patterns and Tumor Microenvironment Infiltration Patterns in Breast Cancer.

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