Molecular characteristics of Chinese colorectal cancer patients with microsatellite instability

Microsatellite instability (MSI) is an important molecular subtype of colorectal cancer (CRC). However, the molecular characteristics of MSI in Chinese patients with CRC remain unclear. The aim of this study was to investigate the molecular characteristics of MSI in Chinese patients with CRC.

A total of 14,239 individuals with CRC were analyzed using tumor tissue and plasma samples for single nucleotide variations (SNVs), insertion-deletions (Indels), copy number variations (CNVs), fusion, MSI, tumor mutational burden (TMB), Epstein-Barr virus (EBV), and homologous recombination deficiency (HRD) using next-generation sequencing (NGS).

The incidence rate of MSI was found to be 7.15%, and patients with microsatellite instability-high (MSI-H) tumors showed variations in age at diagnosis, tumor location, and sample type. TMB was significantly higher in patients with MSI-H tumors than in those with microsatellite stable tumors (MSS) (92.28 vs. 12.07 mutations/Mb, P<0.05), while HRD scores were lower (4.53 vs. 13.5, P<0.05). Additionally, EBV positivity was observed in 0.4% of all patients with CRC, but no patients with positive EBV were detected among those with MSI-H tumors. With regard to genetic mutations, ERBB2, PIK3CA, and BRAF were found to have significantly higher frequencies among patients with MSI-H tumors, whereas APC (51.26% vs. 70.76%, P<0.05), TP53 (27.76% vs. 69.54%, P<0.05), and NRAS (1.86% vs. 3.98%, P<0.05) had higher positive rates among those with MSS tumors. Due to limited germline and epigenetic data, MSI-H tumors could not be classified as Lynch-associated or sporadic.

Overall, MSI-H and MSS CRCs in the Chinese population demonstrate distinct molecular landscapes in terms of TMB, HRD, EBV status, and driver gene alterations, underscoring the molecular heterogeneity of MSI-H CRC and the need for future studies integrating germline and epigenetic data to refine subtype classification.