Mesenteric benign lymph node enlargement in colorectal cancer: Friend or Foe?

Abstract

Abstract Background: Benign lymph node enlargement (BLNE) is common in colorectal cancer; however, few studies have investigatedits influence on prognosis, clinicopathological features, and pathogenesis. Methods: Patients who underwent radical surgery for colorectal cancer at Peking University Third Hospital were grouped according to the presence ofBLNE, and their prognosis and clinical characteristics were analysed. The immune microenvironment and genomic characteristics of primary tumors were comprehensively explored in representative patients. Results: Overall,630 AJCC stage I/IIpatients, with 131 in the BLNE group and 499 in the Non-BLNE (NBLNE) group, were included in the study. Patients in the BLNE group exhibited better disease-free survival (DFS) (hazard ratio [HR] 0.44, P = 0.016) and overall survival (OS) (HR 0.46, P = 0.011) . Interestingly, the prognosis of patients without lymph node metastasis wasworse when the number of harvested lymph nodes was more than 15. On computed tomography (CT) images, significant differences in lymph node morphology were found between BLNE and metastatic lymph node enlargement, including lymph node border, shape and enhancement characteristics. Pathologically, compared with the NBLNE group, the BLNE group had more mature tertiary lymphoid structures (66.7% vs. 36.5%, P = 0.002), greater immunoscore (18.8% vs. 2.1%, P = 0.004) in tumor tissue, and more abundant lymph follicles in lymph nodes (13.69 ± 4.89 vs. 5.08 ± 3.87, P < 0.0001). Whole-exon sequencing analysis revealed greater TMB in the BLNE group [ 6.03 (5.59, 7.59) vs. 5.33 (4.62, 6.34), P = 0.025). 11 differentially mutated genes were identified between the BLNE groupand NBLNE group, with MUC12 (81%) as the most common mutated gene in the BLNE group (odds ratio [OR] 0.10, P = 0.0002). Conclusion: BLNE is a positive factor in predicting the prognosis of colorectal cancer, possibly becausepatients with BLNE have a stronger anti-tumorimmune response. Accurate preoperative lymph node staging is critical.