Image_1_Uncovering the Subtype-Specific Molecular Characteristics of Breast Cancer by Multiomics Analysis of Prognosis-Associated Genes, Driver Genes,.TIF (676.57 kB)
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Image_1_Uncovering the Subtype-Specific Molecular Characteristics of Breast Cancer by Multiomics Analysis of Prognosis-Associated Genes, Driver Genes, Signaling Pathways, and Immune Activity.TIF

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posted on 01.07.2021, 04:51 authored by Xinhui Li, Jian Zhou, Mingming Xiao, Lingyu Zhao, Yan Zhao, Shuoshuo Wang, Shuangshu Gao, Yuan Zhuang, Yi Niu, Shijun Li, Xiaobo Li, Yuanyuan Zhu, Minghui Zhang, Jing Tang

Breast cancer is a heterogeneous malignant disease with different prognoses and has been divided into four molecular subtypes. It is believed that molecular events occurring in breast stem/progenitor cells contribute to the carcinogenesis and development of different breast cancer subtypes. However, these subtype-specific molecular characteristics are largely unknown. In this study, we employed 1217 breast cancer samples from The Cancer Genome Atlas (TCGA) database for a multiomics analysis of the molecular characteristics of different breast cancer subtypes based on PAM50 algorithms. We detected the expression changes of subtype-specific genes and revealed that the expression of particular subtype-specific genes significantly affected prognosis. We also investigated the mutations and copy number variations (CNVs) of breast cancer driver genes and the representative genes of ten signaling pathways in different subtypes and revealed several subtype-specifically altered genes. Moreover, we detected the infiltration of various immune cells in different subtypes of breast cancer and showed that the infiltration levels of major immune cell types are different among these subtypes. Additionally, we investigated the factors affecting the immune infiltration level and the immune cytolytic activity in different breast cancer subtypes, namely, the mutation burden, genome instability and cancer-associated fibroblast (CAF) infiltration. This study may shed light on the molecular events contributing to carcinogenesis and development and provide potential markers and targets for the clinical diagnosis and treatment of different breast cancer subtypes.

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