Comparative genomic signatures in young and old Chinese patients with colorectal cancer

Abstract

Background: Occurrence at a young age is known to be associated with unique clinical features in colorectal cancer (CRC). However, the genomic differences between young and old patients with CRC are not well elucidated and, to the best of our knowledge, have never been investigated in a Chinese population. Methods: Tumor tissue samples from 29 young (age ≤50 years) and 46 old (age >50 years) patients with CRC were collected. Targeted sequencing of 808 cancer-related genes was conducted to characterize the genomic landscape for Chinese CRC. Results: Overall, mutational profiles exhibited notable differences between the two groups. In particular, APC and PIK3CA mutations were more frequently observed in old patients (p = 0.009 and p = 0.012, respectively), while SMAD4 mutations tended to occur in young patients (p = 0.054). Mutation loci distributions of KRAS in the young cohort differed from those in the old cohort, and a higher frequency of KRAS codon 12 mutations was potentially associated with a young age (p = 0.076). The frequencies of clinically actionable alterations were analyzed by defined age categories, which unveiled a distinctive targeted genomic profile in the young group. Furthermore, among patients with mismatch repair-proficient (pMMR) CRC, tumor mutation burden (TMB) was positively correlated with age (Pearson's r = 0.306, p = 0.011), and genomic alterations associated with high TMB in young patients differentiated from those in old patients. Conclusions: These findings revealed different molecular characterization between young and old Chinese patients with CRC, which may provide novel insights for the personalized treatment of CRC.