Multiomics analysis of homologous recombination deficiency across cancer types

Lin Dong; Lin Li; Linyan Zhu; Fei Xu; Rumeng Zhang; Qiushuang Li; Yong Zhu; Zhutian Zeng; Keshuo Ding

doi:10.17305/bb.2024.10448

Authors

Lin Dong Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China https://orcid.org/0000-0002-7207-9825
Lin Li Department of Pathology, Tongling People's Hospital, Tongling, Anhui, China
Linyan Zhu Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
Fei Xu Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China; Department of Pathology, Anhui Provincial Children's Hospital, Hefei, Anhui, China
Rumeng Zhang Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
Qiushuang Li Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
Yong Zhu Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China
Zhutian Zeng Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, University of Science and Technology of China, Hefei, Anhui, China
Keshuo Ding Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China; Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

DOI:

https://doi.org/10.17305/bb.2024.10448

Keywords:

Homologous recombination deficiency (HRD), prognosis, gene mutation, DNA methylation, signaling pathway, immunology

Abstract

There remains ongoing debate regarding the association of homologous recombination deficiency (HRD) with patient survival across various malignancies, highlighting the need for a comprehensive understanding of HRD's role in different cancer types. Based on data from databases, we conducted a multivariable omics analysis on HRD in 33 cancer types, focusing mainly on 23 cancers in which HRD was significantly associated with patient overall survival (OS) rates. This analysis included the mechanisms related to patient prognosis, gene expression, gene mutation, and signaling pathways. In this study, HRD was found to be significantly associated with patient prognosis, but its impact varied among different cancers. HRD was linked to different outcomes for patients with distinct tumor subtypes and was correlated with clinical features such as clinical stage and tumor grade. Driver gene mutations, including TP53, MUC4, KRAS, HRAS, FLG, ANK3, BRCA2, ATRX, FGFR3, NFE2L2, MAP3K1, PIK3CA, CIC, FUBP1, ALB, CTNNB1, and MED12, were associated with HRD across specific cancer types. We also analyzed differentially expressed genes (DEGs) and differentially methylated regions (DMRs) in relation to HRD levels in these cancers. Furthermore, we explored the correlation between HRD and signaling pathways, as well as immune cell infiltration. Overall, our findings contribute to a comprehensive understanding of HRD's multifaceted role in cancer.