The management of stage II colon cancer poses an important clinical challenge due to difficulties in identifying patients at risk of recurrence. RNA expression profiles in solid tissues have demonstrated a strong potential as prognostic markers. The objective of this study was to develop an RNA-based risk score to risk-stratify patients with stage II colon cancer using a large, well-characterized, and screened patient cohort. This multicenter cohort study encompasses tissue samples collected from all surgically resected stage II colon cancer patients in the Region of Southern Denmark from 2014 to 2016 (n = 739). Gene expression analysis was performed on 122 RNAs, previously described as holding prognostic potential in colorectal cancer, using NanoString nCounter analyses. The resulting RNA expression profiles were used to develop a score predicting the risk of recurrence. The primary endpoint for the study was time to recurrence (TTR), with overall survival (OS) as a secondary endpoint. A dichotomized score, derived from the combined expression of four RNAs (ZNF697, SNORA2B, CTSC and OXLD1), effectively predicted TTR in stage II colon cancer patients. The score revealed a hazard ratio (HR) of 6.84 in univariate analysis (p < 0.001) and a HR of 5.00 in multivariate analysis (p < 0.001), surpassing the prognostic performance of known clinical risk factors. Additionally, the score was significantly associated with OS in Kaplan-Meier analysis (p = 0.024). In conclusion, this four-gene expression score demonstrates a strong association with TTR in stage II colon cancer patients, providing valuable prognostic insights that extend beyond conventional clinical risk markers.
© 2025 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
