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.

• Authors: Shuang Guo, Xinyue Wang, Hanxiao Zhou, Yue Gao, Peng Wang, Hui Zhi, Yue Sun, Yangyang Hao, Jing Gan, Yakun Zhang, Jie Sun, Wen Zheng, Xiaoxi Zhao, Yun Xiao, Shangwei Ning
• Journal: Cancers (Cancers (Basel)) Vol. 14 Issue 3 (Jan 25 2022) ISSN: 2072-6694 [Print] Switzerland
• PMID: 35158863 (Publication Type: Journal Article)