K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer

Abstract 

Objective

To determine the prognostic value of K-ras mutations in plasma DNA of unresectable pancreatic cancer patients.

Methods

Blood samples were collected from 91 patients with unresectable pancreatic cancer prior to treatment. K-ras gene was amplified from the circulating plasma DNA. Mutations were detected by direct sequencing. The relationship between the types of K-ras gene and prognosis of unresectable pancreatic cancer was evaluated.

Results

K-Ras codon 12 mutations were found in 30 of 91(33%) plasma DNA samples, 17mutations were c.35G>A (p.G12D), 11 were c.35G>T (p.G12V) and only 2 were c.34G>C (p.G12R)). K-ras codon 12 mutations could significantly reflect the clinical parameters, including TNM tumor staging (P=0.033) and liver metastasis (P=0.014). The median survival time of patients with K-ras mutations was shorter than that of patients with wild-type K-ras gene (3.9 months vs. 10.2 months, P<0.001). K-ras codon 12 mutation from plasma DNA was an independent negative prognostic factor for survival (hazard ratio, 7.39; 95% confidence interval, 3.69–14.89).

Conclusion

K-ras mutation in plasma DNA is a predictive biomarker for a poor prognosis of unresectable pancreatic cancer patients.

Keywords: K-ras gene, Unresectable pancreatic cancer, Survival, Prognostic factors