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Updated: Sep 17, 2025

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Navigating beyond the surface - prognostic significance of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations examined by

Vlad Adrian Afrăsânie1,2, Mihai Vasile Marinca1,2, Bogdan Gafton1,2

  • 1Department of Medical Oncology, Regional Institute of Oncology, Iasi, Romania.

Frontiers in Oncology
|June 27, 2025
PubMed
Abstract

Insights

KRAS exon -3 mutations predict faster progression in metastatic colorectal cancer (mCRC) patients receiving oxaliplatin chemotherapy. TP53 exon 8 mutations, however, correlate with improved overall survival in mCRC.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Metastatic colorectal cancer (mCRC) presents diverse molecular profiles influencing treatment response.
  • Tumor resistance to standard oxaliplatin/fluoropyrimidine chemotherapy is common, necessitating predictive markers.
  • Genomic markers hold potential for prognostic and predictive value in guiding mCRC treatment decisions.

Purpose of the Study:

  • To investigate the prognostic and predictive impact of specific gene mutations in mCRC.
  • To analyze the association of KRAS, NRAS, BRAF, PIK3CA, and TP53 mutations with treatment outcomes in a treatment-naive mCRC population.

Main Methods:

  • Retrospective analysis of 77 mCRC patients treated with oxaliplatin/fluoropyrimidine chemotherapy.
  • Study focused on mutations within KRAS, NRAS, BRAF, PIK3CA, and TP53 genes.
  • Multivariate analysis was employed to assess factors affecting progression-free survival (PFS) and overall survival (OS).

Main Results:

  • Median PFS was 11 months; median OS was 23.6 months.
  • KRAS exon -3 mutations were significantly associated with quicker progression and decreased OS (p=0.03) during oxaliplatin-based chemotherapy.
  • TP53 exon 8 mutations were linked to significantly increased OS (p=0.001).

Conclusions:

  • Specific gene mutations, particularly in KRAS and TP53, have significant prognostic implications in mCRC.
  • Exon-specific mutations within RAS, BRAF, PIK3CA, and TP53 warrant further investigation for therapeutic decision-making.
  • Prospective studies with larger cohorts are needed to validate these findings and their clinical utility.
Keywords:
BRAFKRASNRASPIK3CATP53metastatic colorectal cancerpredictive biomarkersprognostic biomarkers

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