Prognostic Impact of RAS and TP53 Mutation Profiles in Metastatic Colorectal Cancer

TL;DR

This study shows that a specific combination of RAS and TP53 mutations in metastatic colorectal cancer is linked to worse survival outcomes.

Contribution

The study identifies RASm/TP53w as an independent prognostic factor for reduced overall survival in mCRC patients.

Findings

The RASm/TP53w mutation profile had the lowest median progression-free and overall survival.

RASm/TP53w was an independent prognostic factor for decreased overall survival in multivariate analysis.

No significant survival differences were found between RASw/TP53m and RASm/TP53m groups.

Abstract

Background and Objectives: Our study aimed to investigate the effect of RAS and TP53 mutations, either alone or in combination, on survival in patients with metastatic colorectal carcinoma (mCRC). Materials and Methods: Patients diagnosed with mCRC and followed up at our center between January 2019 and November 2023, who underwent somatic mutation analysis via next-generation sequencing (NGS) testing, were retrospectively evaluated. A total of 155 patients were evaluated within the scope of the study. Patients were grouped as mutant type (m) or wild type (w) for RAS and TP53. Survival times between the groups were examined using the Kaplan–Meier method. Cox regression analysis was performed for factors with a prognostic effect on survival. Results: Among the patients, 35.4% exhibited an RASm/TP53w mutation profile, 30.9% had RASw/TP53w, 20% had RASw/TP53m, and 13.5% had RASm/TP53m. The lowest median progression-free survival (mPFS) and median overall survival (mOS) durations were observed in the RASm/TP53w group (7.3 months and 16.9 months, respectively). Median OS was significantly lower in the RASm/TP53w group compared to the RASw/TP53w group (16.9 months vs. 26.0 months, p = 0.003), whereas no significant difference was found between mPFS durations. No statistically significant difference was observed between the RASw/TP53m and RASm/TP53m groups and the RASw/TP53w group for mPFS and mOS. The RASm/TP53w mutation profile was identified as an independent prognostic factor for decreased OS in the multivariate Cox regression analysis. Conclusions: In mCRC cases with the RASm/TP53w mutation profile, the mOS was significantly lower. The RASm/TP53w mutation profile was identified as an independent prognostic factor for decreased OS. These findings are expected to contribute to the literature as real-world evidence regarding the prognostic value of different RAS and TP53 mutation combinations in mCRC.

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