title: dCK Expression and Gene Polymorphism With Gemcitabine Chemosensitivity in Patients With Pancreatic Ductal Adenocarcinoma: A Strobe-Compliant Observational Study.
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.
authors.affiliation: From the Department of Pancreatic Surgery (JX, NK, AL, CT, HZ, XL); State Key Laboratory of Biotherapy and Cancer Center (JT); Department of Thyroid and Breast Surgery (YW); Department of Pathology (DH), West China Hospital, Sichuan University, Chengdu, China; and Department of General Surgery (KA), Warrington and Halton Hospitals, NHS Foundation Trust, Lovely Lane, Warrington, UK.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiong
authors.forename: Kiran
authors.initials: K
authors.lastname: Altaf
authors.forename: Nengwen
authors.initials: N
authors.lastname: Ke
authors.forename: Yichao
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Chunlu
authors.initials: C
authors.lastname: Tan
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Du
authors.initials: D
authors.lastname: He
authors.forename: Xubao
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003842:Deoxycytidine Kinase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine