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Involvement of K-RAS mutations and amino acid substitutions in the survival of metastatic colorectal cancer patients

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Tumor Biology

Abstract

The efficacy of epidermal growth factor-targeting therapies has been found to be limited in tumors with the wild-type K-RAS gene, suggesting a predictive value of K-RAS gene analysis in tumoral response. However, the prognostic value of K-RAS is controversial. This study included patients diagnosed with metastatic colorectal cancer. The presence of K-RAS mutations was analyzed, and the tumors positive for a K-RAS mutation were further analyzed to identify the mutation type. Similarly, the following clinical and pathological variables were also collected. The study was composed of 53.3 % of patients with wild-type K-RAS and 46.7 % of patients with mutated K-RAS (mutated codon 12 was the most frequent). With a mean follow-up of 15 months (range, 1–45), the median survival of patients with wild-type K-RAS was 31.6 months. The median survival was 24.8 months for patients with K-RAS mutated in codon 12 and 17.8 months for patients with mutated codon 13 (p = 0.37). In a univariate analysis, K-RAS was associated with stage IV at diagnosis (p < 0.005). When K-RAS was mutated, a lower overall survival was observed in cases of G→A transition compared with G→T transversion (19.5 vs. 24.2 months, respectively; p = 0.47). When the amino acid change resulted in an acidic substitution, survival was lower, but it increased when the substitution resulted in a polar or nonpolar amino acid (19.5 vs. 23.2 vs. 24.4 months, p = 0.79). The type of K-RAS mutation or amino acid changes may have prognostic implications in metastatic colon cancer patients. Further research is needed in patients treated in prospective controlled trials.

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Authors and Affiliations

  1. Oncology Department, Hospital Costa del Sol, Autovia A-7, Km 187, 29603, Marbella, Spain

    Elisabeth Pérez-Ruiz, A. Rueda, J. Alcaide, R. Villatoro & D. Pérez

  2. Pathological Anatomy Department, Hospital Costa del Sol, Marbella, Spain

    T. Pereda

  3. Molecular Biology Laboratory, Hospital Carlos Haya, Málaga, Spain

    D. Bautista

  4. Department for Support Research: Statistical analysis, REDISSEC, Hospital Costa del Sol, Marbella, Spain

    F. Rivas-Ruiz

  5. Department of Biochemistry, REDISSEC, Hospital Costa del Sol, Marbella, Spain

    M. Redondo

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  1. Elisabeth Pérez-Ruiz
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  2. A. Rueda
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  3. T. Pereda
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  4. J. Alcaide
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  5. D. Bautista
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  6. F. Rivas-Ruiz
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  7. R. Villatoro
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  8. D. Pérez
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  9. M. Redondo
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Correspondence to Elisabeth Pérez-Ruiz.

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Dr. E. Pérez-Ruiz and Dr. A. Rueda belong to REDISSEC.

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Pérez-Ruiz, E., Rueda, A., Pereda, T. et al. Involvement of K-RAS mutations and amino acid substitutions in the survival of metastatic colorectal cancer patients. Tumor Biol. 33, 1829–1835 (2012). https://doi.org/10.1007/s13277-012-0442-z

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  • DOI: https://doi.org/10.1007/s13277-012-0442-z

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