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

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Metastatic colorectal carcinoma (mCRC) survival is influenced by genetic mutations.
• RAS and TP53 mutations are common in mCRC, but their combined prognostic impact requires further elucidation.

Purpose of the Study:

• To investigate the prognostic significance of combined RAS and TP53 mutations in patients with mCRC.
• To determine the effect of specific mutation profiles (RASm/TP53w, RASw/TP53w, RASw/TP53m, RASm/TP53m) on patient survival.

Main Methods:

• Retrospective analysis of 155 mCRC patients who underwent next-generation sequencing (NGS) for somatic mutation analysis.
• Patients were categorized into wild-type (w) or mutant (m) groups for RAS and TP53.
• Survival outcomes (progression-free survival and overall survival) were analyzed using Kaplan-Meier and Cox regression models.

Main Results:

• The RAS-mutant/TP53-wildtype (RASm/TP53w) profile was observed in 35.4% of patients.
• The RASm/TP53w group exhibited the lowest median progression-free survival (7.3 months) and overall survival (16.9 months).
• RASm/TP53w was significantly associated with decreased overall survival compared to RAS-wildtype/TP53-wildtype (RASw/TP53w) (p=0.003) and identified as an independent prognostic factor.

Conclusions:

• The RASm/TP53w mutation profile is associated with significantly reduced overall survival in mCRC patients.
• This specific mutation profile serves as an independent prognostic indicator for poorer outcomes in mCRC.
• These findings provide real-world evidence on the prognostic value of combined RAS and TP53 mutations in mCRC.