Homologous recombination deficiency and immunotherapy response in microsatellite-stable colorectal cancer: Evidence from a cohort study in China

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.