Abstract 262P
Background
The prognostic implications of lymph node metastasis in colorectal cancer patients at an early stage, specifically T1/2 stage, are relatively unfavorable. Therefore, understanding the clinical and molecular traits relevant to metastasis in T1/2 stage are of substantial clinical importance.
Methods
Patients were classified based on their lymph node staging, with an ancillary categorization into MSI-H and MSS subgroups. A comparative mutational study was performed among these groups, incorporating risk stratification and Receiver Operating Characteristic curve analysis, with the aim of discerning the predictability of clinical features integrated with molecular characteristics for early metastasis in T1/2 stage colorectal cancer.
Results
The overall survival and disease-free intervals of T1/2N+ patients were considerably inferior compared to T1/2N- patients. Vascular infiltration, low level of tumor differentiation, and unfavorable histological type correlated significantly with early lymph node metastasis. A higher proportion (10.6%) of MSI-H cases was observed in T1/2N+ patients. Mutational profiling disclosed substantial enrichment of TSC2, RECQL4, and LRP1B mutations in T1/2N+ patients, predominantly those with MSS phenotype. Besides, a higher tumor mutational load, especially in the MSI-H subtype was apparent in T1/2N+ patients. Finally, a nomogram integrating specific mutations with other clinical risk attributes resulted in markedly enhanced prediction accuracy.
Conclusions
Lymph node metastasis in early-stage colorectal cancer demonstrates a unique molecular signature typified by vascular infiltration, presence of micro-residual lesions, and mutations in TSC2, RECQL4, and LRP1B. Factors such as inferior tumor differentiation and histological type augment the risk for lymph node metastasis at the early stage.
Clinical trial identification
NCT06238193.
Legal entity responsible for the study
The authors.
Funding
This work was supported by the National Natural ScienceFoundation (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
All authors have declared no conflicts of interest.