Genomic Signatures of Recurrence After Resection of Early-Stage Node-Negative Colon Cancer

Whereas clinicopathologic risk factors for colon cancer (CC) recurrence are well-established, the role of genomic predictors remains understudied. This study aimed to identify genomic factors associated with recurrence after resection of early-stage, node-negative CC.

A retrospective cohort study was performed using clinicopathologic data, somatic mutations, and mRNA expression profiles from the cBioPortal database. The study enrolled patients with T1-3, N0, or M0 CC who underwent surgical resection and primary tumor sequencing. Those with fewer than 6 months of follow-up evaluation were excluded. Gene expression profiles were classified into consensus molecular subtypes (CMSs). Somatic mutations and CMS groups were analyzed for associations with recurrence.

Of the 305 patients analyzed, 46 (15%) experienced recurrence. The median age at diagnosis was 70 years (interquartile range [IQR], 62-76 years), the gender distribution was balanced. The median follow-up period was 38 months, and the median time to recurrence was 13 months. The following 12 mutated genes were significantly associated with recurrence: KRAS (odds ratio [OR], 2.19), PIK3CA (OR, 2.13), DNAH11 (OR, 3.28), NALCN (OR, 4.69), COL6A3 (OR, 3.12), GRIN2A (OR, 4.92), COL6A1 (OR, 4.25), TNN (OR, 3.25), NEXMIF (OR, 6.97), PKHD1L1 (OR, 3.24), CDH4 (OR, 3.29), and BCL9 (OR, 4.03). Additionally, tumors classified as CMS4/mesenchymal subtype had a greater risk of recurrence (OR, 4.67) than the CMS2/canonical subtype. Patients with CMS4 or at least four mutations associated with recurrence (n = 77) had a 5-year disease-free survival rate of 57.7%.

This study identified novel genomic signatures that may improve risk stratification in early-stage node-negative CC, potentially guiding the selection of high-risk patients for adjuvant therapy.