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Background <p>The oncologic significance of specific <i>KRAS</i> point mutations for patients with colorectal liver metastases (CLM) is uncertain. This study aimed to assess the prognostic impact of <i>KRAS</i> point mutations on patients who underwent surgery for CLM.</p> Methods <p>Patients who underwent curative-intent surgery for CLM from 2001 to 2020 were selected for the study. In the study, <i>KRAS</i> point mutations and other clinicopathologic variables were examined for association with survival.</p> Results <p>The study classified 798 patients into five groups by <i>KRAS</i> mutation status as follows: wild-type (<i>n</i> = 412, 51.6%), G12D (<i>n</i> = 123, 15.4%), G12V (<i>n</i> = 88, 11.0%), G13D (<i>n</i> = 61, 7.6%), and “Other” mutations (<i>n</i> = 114, 14.3%). For the patients with G12V substitutions, <i>TP53</i> mutation was associated with worse overall survival (OS) (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.04–6.66; <i>P</i> = 0.041), but was not associated with a survival difference for the other four groups. The patients with co-occurring <i>KRAS</i> G12V and <i>TP53</i> had a median OS of 4.4 years and a 5-year OS rate of 39.8%. In contrast, the patients with <i>KRAS</i> G12V mutation and wild-type TP53 had a median OS of 7.3 years and a 5-year OS rate of 75.9%, similar to the corresponding values for the patients with wild-type <i>KRAS</i>. Co-occurring <i>KRAS</i> G12V and <i>TP53</i> mutations were independently associated with worse OS in the entire cohort (HR, 2.08; 95% CI, 1.15–3.76; <i>P</i> = 0.015).</p> Conclusions <p>This study showed that <i>KRAS</i> G12V mutation is associated with worse OS for patients undergoing curative-intent CLM resection, but only those with co-occurring <i>TP53</i> mutation. Prognosis after surgery for CLM should not be stratified by <i>KRAS</i> mutation site alone.</p>

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Associations of KRAS Point Mutations with Survival of Patients Who Underwent Curative-Intent Resection of Colorectal Liver Metastases

  • 期刊论文

  • 发表日期：

    2025年1月16日

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  • Harufumi Maki,
  • Reed I. Ayabe,
  • Antony Haddad,
  • Yujiro Nishioka,
  • Timothy E. Newhook,
  • Hop S. Tran Cao,
  • Yun Shin Chun,
  • Ching-Wei D. Tzeng,
  • Jean-Nicolas Vauthey

摘要

Background

The oncologic significance of specific KRAS point mutations for patients with colorectal liver metastases (CLM) is uncertain. This study aimed to assess the prognostic impact of KRAS point mutations on patients who underwent surgery for CLM.

Methods

Patients who underwent curative-intent surgery for CLM from 2001 to 2020 were selected for the study. In the study, KRAS point mutations and other clinicopathologic variables were examined for association with survival.

Results

The study classified 798 patients into five groups by KRAS mutation status as follows: wild-type (n = 412, 51.6%), G12D (n = 123, 15.4%), G12V (n = 88, 11.0%), G13D (n = 61, 7.6%), and “Other” mutations (n = 114, 14.3%). For the patients with G12V substitutions, TP53 mutation was associated with worse overall survival (OS) (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.04–6.66; P = 0.041), but was not associated with a survival difference for the other four groups. The patients with co-occurring KRAS G12V and TP53 had a median OS of 4.4 years and a 5-year OS rate of 39.8%. In contrast, the patients with KRAS G12V mutation and wild-type TP53 had a median OS of 7.3 years and a 5-year OS rate of 75.9%, similar to the corresponding values for the patients with wild-type KRAS. Co-occurring KRAS G12V and TP53 mutations were independently associated with worse OS in the entire cohort (HR, 2.08; 95% CI, 1.15–3.76; P = 0.015).

Conclusions

This study showed that KRAS G12V mutation is associated with worse OS for patients undergoing curative-intent CLM resection, but only those with co-occurring TP53 mutation. Prognosis after surgery for CLM should not be stratified by KRAS mutation site alone.