K-Ras mutation in liquid biopsy and tumor tissue correlation in patients with pancreatic cancer

Abstract

Introduction: K-Ras mutation plays an important aspect in the outcome and prognostic in pancreatic cancer, and its role in its carcinogenesis is critical. For this reason, early detection is of utmost importance. Circulating biomarkers have potential as a monitoring and diagnostic tool for pancreatic cancer and cell-free circulating tumor DNA (ctDNA) in plasma has been considered a useful candidate for non-invasive cancer diagnosis. This current study was designed to estimate the clinical benefits of ctDNA using BEAMing digital polymerase chain technology in patients with pancreatic cancer. Methods: This was an observational study that included 40 patients with histological confirmed pancreatic cancer referred to the Medical Oncology department from Reina Sofia Hospital of Córdoba, from June 2017 until February 2019. We assessed K-ras mutation from formalin fixed paraffin embedded tissue DNA using PCR and ctDNA in serum sample using BEAMing digital polymerase chain and compared K-Ras mutations in both settings. Data was collected and analyzed using SPPS v23 program. Results: The median age was 62 years. Metastatic patients were predominant (29/40), localized advanced (7/40), and local pancreatic cancer (4/40). We identified K-ras mutations in 72.5% of the biopsy tissue (29/40) and 55% in serum samples (22/40) in this cohort. Both sexes were equally distributed with 20 patients each. Men had the same amount of K-ras mutations (14/20) in both settings, with a concordance rate of 78.6%.Women's ctDNA K-ras mutation were significantly lower (8/20) but the concordance rate was higher than men with 87.5%. In patients with oligometastatic disease (< 2 organs) the concordance rate was lower (76.5%) in comparison with multiple metastases (100%). The overall concordance rate between K-ras mutation in biopsy tissue and plasma serum was 81.8%. Statistical significance was achieved in the concordance rate in patients with metastatic disease (p=0.037), in comparison to patients with localized disease. Survival was significantly shorter of patients with K-ras mutations in both ctDNA and biopsy tissue than of patients without mutations, although statistical significance was not achieved. Conclusion: Liquid biopsy (ctDNA) is a useful procedure for detecting K-ras mutations in patients with pancreatic cancer. Patients with higher tumor burden have additional benefits in the detecting KRAS mutation in ctDNA.