ABSTRACT
OBJECTIVE: The objectives of the study are to investigate the sensitivity and specificity of circulating tumor DNA (ctDNA) for the diagnosis of pancreatic cancer and to assess the utility of ctDNA as a prognostic marker in this disease. METHODS: Cell-free DNA was extracted from plasma of patients who underwent endoscopic ultrasound fine-needle aspiration or surgical resections for pancreatic cancer. The cell-free DNA was then analyzed using droplet digital polymerase chain reaction for KRAS G12/13 mutations. Eighty-one patients with pancreatic cancer and 30 patients with benign pancreatic disease were analyzed. RESULTS: ctDNA KRAS G12/13 mutations were detected in 63% of all patients with pancreatic cancer and in 76% of those patients who also had KRAS G12/13 mutations detected in the pancreatic primary. Specificity and tissue concordance were both 100%. Circulating tumor DNA corresponded with tumor size and stage, and high ctDNA was associated with significantly worse prognosis on both univariate and multivariate testing. CONCLUSION: Our study shows that ctDNA is an accurate diagnostic tool and strong prognostic marker in patients with pancreatic cancer. The continued investigation of ctDNA will enable its implementation in clinical practice to optimize the care and survival outcomes of patients with pancreatic cancer.
Subject(s)
Circulating Tumor DNA , Pancreatic Neoplasms , Humans , Circulating Tumor DNA/genetics , Prognosis , Proto-Oncogene Proteins p21(ras)/genetics , Biomarkers, Tumor/genetics , Mutation , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic NeoplasmsABSTRACT
Sprouty (Spry) proteins, modulators of receptor tyrosine kinase signaling pathways, have been shown to be deregulated in a variety of pathological conditions including cancer. In the present study we investigated the expression of Spry1 and Spry2 isoforms in a panel of human ovarian cancer cell lines in vitro. Our western blot analysis showed nonuniform patterns of Spry expression in the cancer cells, none of which conformed to the pattern observed in the normal ovarian epithelial cells employed as the control. Among the seven cancer cell lines studied, Spry1 was expressed lower in four cell lines and higher in one as compared with the control. As for Spry2, four cell lines showed lower and two exhibited higher expression. Results from RT-PCR assay raised the possibility that Spry protein levels may not necessarily correspond with its expression at mRNA level. Our immunostaining study revealed that Spry2 was predominantly distributed within the whole cytoplasm in vesicular structures whereas Spry1 was found in both the cytoplasm and nucleus. This might provide clues to further investigation of Spry mode of action and/or function. Collectively, our study unveiled the differential expression of Spry1 and Spry2 proteins in various ovarian cancer cell lines.
