Risk factors for lateral lymph node metastasis based on the molecular profiling of rectal cancer.

Aim: The association between molecular profiles and lateral lymph node metastasis (LLNM) in patients with rectal cancer remains unclear. Therefore, this study aimed to identify the molecular profiles of rectal cancer associated with LLNM.

Method: We retrospectively examined patients who underwent rectal cancer surgery with lateral lymph node dissection without preoperative treatment and whose surgically resected specimens were evaluated using multiomics-based analyses from 2014 to 2019. We compared the clinical characteristics and molecular profiles of patients with pathological LLNM (pLLNM+) with those of patients without (pLLNM-) and identified risk factors for LLNM.

Results: We evaluated a total of 123 patients: 18 with and 105 without pLLNM. The accumulation of mutations in genes key for the development of colorectal cancer were similar between the groups, as was the tumour mutation burden. The distribution of consensus molecular subtypes (CMS) was significantly different between the groups (p = 0.0497). The pLLNM+ patients had a higher prevalance of CMS4 than the pLLNM- patients (77.8% vs. 51.4%). According to the multivariate analysis, the independent risk factors for LLNM were a short-axis diameter of the lateral lymph node of ≥6.0 mm and CMS4; furthermore, the presence of either or both had a sensitivity of 100% for the diagnosis of LLNM.

Conclusion: Lateral lymph node size and CMS4 are useful predictors of LLNM. The combination of CMS classification and size criteria was remarkably sensitive for the diagnosis of LLNM.