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

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. (C) 2010 Elsevier Ltd. All rights reserved.