Clinicopathological, Prognostic, and Molecular Differences Between Microsatellite-Stable Colorectal Cancer Patients Aged ≤ 30 Years and >30 Years

Background The biological and clinical heterogeneity of younger patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) colorectal cancer (CRC) is largely unexplored. This retrospective study compared the clinicopathological factors, prognosis, and molecular characteristics of MSS/pMMR CRC in patients younger and older than 30 years. Methods Overall, 191 and 573 younger (≤ 30 years old) and older (> 30 years old) CRC patients, respectively, were enrolled. Statistically significant differences between the groups were determined using the χ ² or Fisher's exact test. Progression-free survival (PFS) was assessed by Kaplan-Meier analysis and compared using log-rank test. Results Younger patients with MSS/pMMR CRC exhibited significantly more aggressive features, including higher rates of mucinous adenocarcinoma, poor differentiation, deeper tumour invasion and advanced tumour–node–metastasis (TNM) stage than older patients. Molecular analysis revealed a higher microsatellite instability-high (MSI-H) incidence but lower KRAS mutation frequency in younger patients compared to older individuals. Furthermore, comprehensive genetic profiling of 1021 genes revealed no additional significant variations and no significant differences in PFS between the two MSS/pMMR CRC groups. Conclusion Younger patients with CRC exhibit unique biological behaviour. Therefore, unravelling the mechanisms of its aggressiveness through integrated multi-omics technologies should be a key focus in future research.