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. Overall, 191 younger (≤ 30 years old) and 892 older (> 30 years old) CRC patients were enrolled. Statistically significant differences between the groups were determined using the χ2 or Fisher’s exact test. Progression-free survival (PFS) was assessed by Kaplan–Meier analysis and compared using log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. 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. Among all CRC patients, molecular analysis revealed a higher microsatellite instability-high incidence but lower KRAS mutation frequency in younger patients compared with in older individuals. Comprehensive genetic profiling of 1021 genes revealed no additional significant variations between the two MSS/pMMR CRC groups. Survival analysis showed that younger patients with MSS/pMMR CRC had significantly shorter PFS than older patients (log-rank P < 0.001), although multivariate analysis indicated that age was not an independent prognostic factor. 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.
Wang et al. (2026) studied this question.