dCK Expression and Gene Polymorphism With Gemcitabine Chemosensitivity in Patients With Pancreatic Ductal Adenocarcinoma

Abstract

The aim of this study was to investigate the relationship of deoxycytidine kinase (dCK) protein expression and gene single-nucleotide polymorphisms to gemcitabine chemosensitivity in patients with pancreatic ductal adenocarcinoma (PDAC).In total, 54 patients with resectable PDAC, who received postoperative gemcitabine-based therapy, were enrolled in this study, from January 2011 to April 2013. The dCK protein expression was measured retrospectively by immunohistochemistry. Furthermore, 5 single-nucleotide polymorphisms (C1205T, A9846G, A70G, C356G, and C364T) of the dCK gene were detected in PDAC cells by PCR amplification and sequencing.The dCK protein expression was found to be negatively correlated with age (P = 0.006), but correlated positively with overall survival (OS) (P = 0.000) and disease-free survival (DFS) (P = 0.003). The A9846G AA genotype in the dCK gene was significantly associated with reduced mortality compared with AG and GG genotypes. The OS and DFS were longer in patients with the A9846G AA genotype than the AG and GG genotypes. In univariate and multivariate analyses, we found that the dCK protein expression and A9846G genotype were significant predictors of both OS and DFS.Our study suggests that the dCK protein expression and A9846G genotype may act as prognostic biomarkers in identifying patients who are likely to benefit from postoperative gemcitabine therapy in PDAC.

Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma

“…32 In line with the essential roles of hENT1 and dCK in gemcitabine metabolism, the hENT1 knockdown in biliary tract cancer cells 20 and dCK knockdown in pancreatic cancer cells 19 attenuated cell sensitivity to gemcitabine, which is consistent with the present results. High expression levels of hENT1 or dCK were associated with better survival in gemcitabine-treated cholangiocarcinoma 20 , 21 and pancreatic cancer, 17 , 18 , 22 , 23 indicating that the functional roles of hENT1 and dCK in vitro reflect their roles in gemcitabine sensitivity in clinical settings. Therefore, the present results demonstrated that patients with meningiomas expressing high levels of hENT1 and dCK may benefit from gemcitabine-based chemotherapy and, thus, clinical trials to test the efficacy of gemcitabine in high-grade meningiomas are warranted.…”

DCK expression, a potential predictive biomarker in the adjuvant gemcitabine chemotherapy for biliary tract cancer after surgical resection: results from a phase II study

“…The pharmacological activity of these nucleoside analogs is dependent on phosphorylation by DCK [ 20 ]. The expression of the dCK gene and protein and single-nucleotide SNPs in the dCK gene have been closely associated with gemcitabine chemosensitivity in patients with pancreatic cancer [ 21 – 23 ]. By employing immunohistochemistry, a small retrospective study found that high levels of dCK protein expression correlated positively with OS in pancreatic cancer patients undergoing adjuvant gemcitabine chemotherapy [ 21 , 24 ].…”

Prognostic value of combined preoperative lactate dehydrogenase and alkaline phosphatase levels in patients with resectable pancreatic ductal adenocarcinoma

“…[ 2 ] Sixty to seventy percent of newly diagnosed pancreatic cancer patients present with advanced disease. The 5-year survival among these patients is only 5% to 7%, [ 3 , 4 ] and the vast majority of patients survive less than 1 to 2 years. Even following curative surgery, 90% of patients progress in 12 to 18 months.…”