Molecular Characteristics of Early-onset Compared With Late-onset Colorectal Cancer

The prognosis of early-onset colorectal cancer (EOCRC) is worse than that of late-onset colorectal cancer (LOCRC), and the incidence has gradually increased in recent years, so it is necessary to study the pathogenesis and explore the target of early-onset colorectal cancer patients. In this study, investigators aimed to explore the specific molecular pathologic map of EOCRC by comparing LOCRC. This study enrolled 11,344 patients with colorectal cancer treated at the Colorectal Center of the First Affiliated Hospital of Nanjing Medical University from 2003 to 2022, of whom 578 were EOCRC and 10,766 were LOCRC. The tumor-related mutation status and tumor mutation burden (TMB) of patients were detected by next-generation sequencing technology. PD-L1 expression was detected by immunohistochemistry. The microsatellite instability was detected by polymerase chain reaction (PCR) coupled with capillary electrophoresis (2B3D NCI Panel) in all patients. Among the 11,344 patients, 180 patients with EOCRC and 90 patients with LOCRC patients underwent NGS investigation. Compared with LOCRC, EOCRC patients generally presented a later TNM stage, lower tumor differentiation, and poorer histological type. In LOCRC with MSI-H stupe, TNM stage is earlier than whom with MSI-L/MSS. In addition, the frequency of MSI-H was significantly higher in EOCRC (10.2%) than LOCRC (2.2%). The frequency of 7-mutation panel (ARID1A, FANCI, CASP8, DGFRA, DPYD, TSHR, and PRKCI) were relatively higher in LOCRC. In EOCRC group, the TNM stage of MSI-H subtype patients was earlier while harbored with worse tissue differentiation and higher proportion of mucinous adenocarcinoma. Besides, among the EOCRC patients, FBXW7, FAT1, ATM, ARID1A and KMT2B mutation frequencies were significantly increased in patients with MSI-H type. Comparing with MSI-H patients of LOCRC, the EOCRC patients with MSI-H presented a higher mutation frequencies of FGFBR2, PBRM1, RNF43, LRP1B, FBXW7, ATM and ARID1A. In addition, EOCRC patients were identified with higher tumor mutation burden, especially in the MSI-H type. PD-L1 expression calculated by tumor proportion score (TPS) was also elevated in EOCRC and correlated with MSI status.