Page 40 - TD-4-3

Tumor Discovery

ORIGINAL RESEARCH ARTICLE
Genomic alterations of homologous

recombination deficiency in Chinese NSCLC patients

Shuang Xiang 1† , Changqiong Shen 2† , Chun Huang 3 , Ya-ting Yang 1 ,
Jing Guo 4 , Yi Liu 5 , Mingzhu Yin * , and Song Duan *
1
1
1 Department of Pathology, Chongqing University Three Gorges Hospital, Chongqing, China
2 Department of Radiology, People’s Hospital Affiliated to Chongqing Three Gorges Medical College,
Chongqing, China
3 Department of Respiratory Medicine, Chongqing University Three Gorges Hospital, Chongqing,
China
4 Department of Oncology, Chongqing University Three Gorges Hospital, Chongqing, China
5 Department of Thoracic Surgery, Chongqing University Three Gorges Hospital, Chongqing, China
(This article belongs to the Special Issue: New Developments in Lung Cancer Research, Diagnosis,
Treatment, and Prognosis)

Abstract

Homologous recombination deficiency (HRD) affects genomic stability and has
† These authors contributed equally potential as a biomarker for the effectiveness of poly (ADP-ribose) polymerase (PARP)
to this work. inhibitors and immune checkpoint inhibitors. However, the clinical and molecular profile
*Corresponding authors: of HRD in non-small cell lung cancer (NSCLC), particularly in the Chinese population,
Mingzhu Yin remains poorly characterized. Based on the next-generation sequencing data of 158
(yinmingzhu2008@126.com) Chinese NSCLC patients, we analyzed the HRD scores of mutations in homologous
Song Duan
(duansong2024@163.com) recombination repair (HRR) genes and dissected the correlation between HRD state
and programmed death-ligand 1 (PD-L1) expression. Alterations in HRR genes were
Citation: Xiang S, Shen C,
Huang C, et al. Genomic alterations observed in 8.9% of the patients, with ATM and BRCA2 being the most commonly
of homologous recombination affected genes. HRD-high (HRD-H) status was significantly associated with advanced
de iciency in Chinese NSCLC disease stage (≥III) and lung squamous cell carcinoma (LUSC). Transcriptomic analysis
patients. Tumor Discov.
2025;4(3):32-45. revealed distinct gene expression profiles between HRD-H and HRD-low (HRD-L)
doi: 10.36922/TD025180032 subgroups, with HRD-H tumors exhibiting predominantly downregulated genes. While
EGFR mutations occurred at similar frequencies across HRD status, TP53 mutations
Received: April 30, 2025
were significantly enriched in HRD-H cases. HRD-H status correlated with higher PD-L1
Revised: May 20, 2025 positivity in NSCLC overall, but not within the lung adenocarcinoma (LUAD) subgroup in
Accepted: May 21, 2025 our cohort. The Cancer genome atlas analysis showed higher PD-L1 protein expression
in HRD-H LUAD, but not in LUSC. Kyoto Encyclopedia of Genes and Genomes analysis
Published online: June 6, 2025
identified enrichment of complement and coagulation cascades, ABC transporters,
Copyright: © 2025 Author(s). and bile secretion pathways in HRD-H tumors, suggesting links to immune evasion
This is an Open-Access article
distributed under the terms of the and drug resistance. This study elucidates the genomic landscape of HRD in Chinese
Creative Commons Attribution NSCLC patients and provides insights into its potential clinical utility for therapeutic
License, permitting distribution, targeting. Our findings suggest that integrated HRD scoring may guide the application
and reproduction in any medium,
provided the original work is of PARP inhibitors and immunotherapy in specific NSCLC patient subgroups. Further
properly cited. prospective clinical studies are needed to validate the predictive value of HRD scoring
Publisher’s Note: AccScience in NSCLC treatment and to optimize patient selection strategies.
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Homologous recombination deficiency; Immunotherapy biomarkers;
affiliations. Next-generation sequencing; Non-small cell lung cancer; Programmed death-ligand 1

Volume 4 Issue 3 (2025) 32 doi: 10.36922/TD025180032