Clinicopathological, prognostic, and molecular differences between microsatellite-stable colorectal cancer patients...

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.