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Homologous repair deficiency-associated genes in invasive breast cancer revealed by WGCNA co-expression network analysis and genetic perturbation similarity analysis by Haohao Chen; Yanyan Liu; Zhenglang Yin; Hao Chen; Yao Wang; Yeben Qian is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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ABSTRACT Background: Homologous repair deficiency (HRD) causes double-strand break repair to be impeded, which is a common driver of carcinogenesis. However, the therapeutic and prognostic potential of HRD in invasive breast cancer (BRCA) has not been fully explored using comprehensive bioinformatics analysis. Materials and Methods: HRD score was defined as the unweighted sum of LOH, TAI, and LST scores and obtained from the previous study according to Theo A et al. To characterize BRCA tumor microenvironment (TME) subtypes, “ConsensusClusterPlus” R package was used to conduct unsupervised clustering. The xCell algorithm was utilized for tumor composition analysis to estimate the TME in TCGA-BRCA. A WGCNA analysis was conducted to uncover the gene coexpression modules and hub genes in the HRD-related gene module of BRCA. The functional enrichment study was carried out using Metascape. A novel analysis pipeline, Genetic Perturbation Similarity Analysis (GPSA), was used to explore the single-gene perturbation closely related to HRD based on 3048 stable knockdown/knockout cell lines. The prognostic variables were evaluated using univariate COX analysis. Kaplan-Meier (KM) survival anal

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Author

Haohao Chen; Yanyan Liu; Zhenglang Yin; Hao Chen; Yao Wang; Yeben Qian

Publisher

Informa UK Limited

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)