Retrospective Cohort Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2025; 17(5): 102767
Published online May 15, 2025. doi: 10.4251/wjgo.v17.i5.102767
Homologous recombination deficiency and immunotherapy response in microsatellite-stable colorectal cancer: Evidence from a cohort study in China
Hao Feng, Li-Ying Zhao, Zhou Xu, Qing-Feng Xie, Hai-Jun Deng, Jiang Yu, Hao Liu
Hao Feng, Li-Ying Zhao, Zhou Xu, Qing-Feng Xie, Hai-Jun Deng, Jiang Yu, Hao Liu, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Co-first authors: Hao Feng and Li-Ying Zhao.
Co-corresponding authors: Jiang Yu and Hao Liu.
Author contributions: Deng HJ, Liu H and Yu J conceived and designed the study; Feng H, Xu Z, and Xie QF acquired the data; Feng H and Zhao LY implemented quality control of data and the algorithms; Feng H and Zhao LY did the statistical analyses; Feng H prepared the first draft of the manuscript. All authors analyzed and interpreted the data. All authors contributed to manuscript preparation. All authors have read and approve the final manuscript. Feng H and Zhao LY contributed equally to this work as co-first authors. Yu J and Liu H are designated as co-corresponding authors due to their significant and equal contributions to the research and manuscript. Both authors have played pivotal roles in the study design, data analysis, and interpretation of results, ensuring the integrity and accuracy of the research findings. Yu J, as a senior expert in the field of oncology, provided invaluable insights into the clinical aspects of colorectal cancer (CRC), particularly in the context of microsatellite-stable (MSS) CRC patients and homologous recombination deficiency (HRD). He has been deeply involved in the clinical trial design, patient selection, and the interpretation of immunotherapy responses in MSS CRC, making him a crucial contributor to the study. Liu H took primary responsibility for the design and execution of the molecular genetic analyses, including next-generation sequencing, and the integration of the genetic data with clinical outcomes. His expertise in bioinformatics and genomic instability further enriched the research, providing robust evidence for the potential predictive role of HRD in MSS CRC patients' response to immunotherapy. Both authors shared equal responsibility in drafting, revising, and finalizing the manuscript, ensuring its scientific rigor and coherence. Their combined expertise in both clinical and molecular aspects of CRC has been fundamental to the successful execution of this study, warranting their joint designation as co-corresponding authors.
Supported by Natural Science Foundation of Guangdong Province, No. 2021A1515011146 and No. 2023A1515010785; and Key Areas Research and Development Programs of Guangdong Province, No. 2023B1111050009.
Institutional review board statement: This retrospective study was approved by the Ethics Committee of Nanfang Hospital of Southern Medical University (Guangzhou, China) (ID: NFEC-2021-396).
Informed consent statement: Patient consent was waived because all patient data was de-identified.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Pathology data and the statistical analyses for the current study are available from the corresponding author at liuhaofbi@163.com upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hao Liu, MD, PhD, Professor, Department of General Surgery, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave. North, Guangzhou 510515, Guangdong Province, China. liuhaofbi@163.com
Received: November 5, 2024
Revised: February 14, 2025
Accepted: March 7, 2025
Published online: May 15, 2025
Processing time: 193 Days and 19.3 Hours
Abstract
BACKGROUND

Patients with colorectal cancer (CRC) exhibiting microsatellite instability (MSI)-high generally demonstrate a favorable response to immunotherapy. In contrast, the efficacy of immunotherapy in microsatellite-stable (MSS) CRC patients is considerably restricted. This study sought to evaluate the effectiveness of immunotherapy in MSS patients characterized by homologous recombination deficiency (HRD) as opposed to those with homologous recombination proficiency (HRP).

AIM

To investigate and compare the clinicopathological characteristics, treatment modalities, and outcomes between the HRD and HRP groups in CRC.

METHODS

Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status. Patients with HRD-related gene alterations or an HRD score ≥ 30 were classified into the HRD group, while the remaining patients were assigned to the HRP group. Clinical data, including staging and treatment regimens, were collected for analysis. Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment.

RESULTS

Among the 268 patients, 64 were classified into the HRD group, which had a higher proportion of early-stage CRC diagnoses compared to the HRP group. Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts, as well as among MSS patients treated with immunotherapy (P < 0.05).

CONCLUSION

This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.

Keywords: Colorectal cancer; Homologous recombination deficiency; Microsatellite-stable; Prognosis; Immunotherapy

Core Tip: This study evaluates the effectiveness of immunotherapy in microsatellite-stable (MSS) colorectal cancer (CRC) patients with homologous recombination deficiency (HRD). By analyzing 268 CRC patients through next-generation sequencing, the research identifies a significant correlation between HRD status and improved survival outcomes. Notably, MSS patients with HRD exhibited better prognoses when treated with immunotherapy compared to those with homologous recombination proficiency. These findings suggest that HRD status may serve as a critical predictive marker for immunotherapy response in MSS CRC patients.