Abstract 132P
Background
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, we aimed to explore the specific molecular pathologic map of EOCRC by comparing LOCRC.
Methods
This study enrolled 11,344 patients with colorectal cancer from 2003 to 2022. The tumor-related mutation status and tumor mutation burden of patients were detected by next-generation sequencing technology. PD-L1 expression was detected by immunohistochemistry. The microsatellite instability was detected by coupled with capillary electrophoresis (2B3D NCI Panel) in all patients.
Results
When comparing LOCRC with EOCRC patients, it was observed that the latter generally presented with a later TNM stage, lower tumor differentiation, and a poorer histological type. In LOCRC patients with MSI-H status, the TNM stage was earlier compared to those with MSI-L/MSS status. Moreover, the incidence of MSI-H was significantly higher in EOCRC (10.2%) compared to LOCRC (2.2%). The prevalence of mutations in the 7-gene panel (ARID1A, FANCI, CASP8, DGFRA, DPYD, TSHR, and PRKCI) was relatively higher in LOCRC. Within the EOCRC group, patients with the MSI-H subtype exhibited an earlier TNM stage but harbored worse tissue differentiation and a higher proportion of mucinous adenocarcinoma. Among EOCRC patients, mutation frequencies of FBXW7, FAT1, ATM, ARID1A, and KMT2B were significantly increased in those with MSI-H status. Comparing MSI-H patients of LOCRC with EOCRC patients revealed higher mutation frequencies of FGFBR2, PBRM1, RNF43, LRP1B, FBXW7, ATM, and ARID1A in the latter. Additionally, EOCRC patients exhibited a higher tumor mutation burden, particularly in the MSI-H subtype. PD-L1 expression, assessed by tumor proportion score (TPS), was also elevated in EOCRC and correlated with MSI status.
Conclusions
The distribution rate of MSI-H was significantly higher in EOCRC, and has a specific mutational profile and relatively high PD-L1 expression, which may be used to guide personalized treatment to better control the disease.
Clinical trial identification
NCT06238193.
Legal entity responsible for the study
The author.
Funding
National Natural Science Foundation (Grant Number 82100617, 82273406); Nature Key Research and Development Program of Jiangsu Province (BE2021742); Basic Research Program of Jiangsu Province (BK20201491, BK20221415); National Key Research and Development Program of China (2017YFC0908200); Jiangsu Key Medical Discipline (General Surgery; Grant No. ZDxKA2016005).
Disclosure
The author has declared no conflicts of interest.