Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma

Abstract

BACKGROUND: Gemcitabine (2 0 ,2 0 -difluorodeoxycytidine) administration after resection of pancreatic cancer improves both disease-free survival (DFS) and overall survival (OS). Deoxycytidine kinase (dCK) mediates the ratelimiting catabolic step in the activation of gemcitabine. The authors of this report studied patient outcomes according to the expression of dCK after a postoperative gemcitabine-based chemoradiation regimen. METHODS: Fortyfive patients with resected pancreatic adenocarcinoma received adjuvant gemcitabine based-therapy in the context of multicenter phase 2 studies. Their tumors were evaluated retrospectively for dCK protein expression by immunohistochemistry. A composite score based on the percentage of dCK-positive cancer cells and the intensity of staining was generated, and the results were dichotomized at the median values. RESULTS: The median follow-up was 19.95 months (95% confident interval [CI], 3.3-107.4 months). The lymph node (LN) ratio and dCK protein expression were significant predictors of DFS and OS in univariate analysis. On multivariate analysis, dCK protein expression was the only independent prognostic variable (DFS: hazard ratio [HR], 3.48; 95% CI, 1.66-7.31; P ¼ .001; OS: HR, 3.2; 95% CI,1.44-7.13; P ¼ .004). CONCLUSIONS: dCK protein expression was identified as an independent and strong prognostic factor in patients with resected pancreatic adenocarcinoma who received adjuvant gemcitabine therapy. The authors concluded that it deserves prospective evaluation as a predictive biomarker for patient selection. Cancer 2010;116:5200-6.

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

“…27 They also categorically demonstrated that a low dCK expression was an independent risk factor for recurrence and mortality. Two recent retrospective studies have also signified the fact that a preoperative high level of dCK protein is able to predict patient response to gemcitabine and is associated with an improved outcome for these patients in way of increased OS.…”

Vasohibin 2 reduces chemosensitivity to gemcitabine in pancreatic cancer cells via JUN proto-oncogene dependent transactivation of ribonucleotide reductase regulatory subunit M2

“…The expression of these nucleoside transporters is correlated with chemosensitivity and patient survival [19][20][21][22][23]. After being taken into the cells, gemcitabine is activated by deoxycytidine (dCK) [24,25]. Thus, hENT1, hCNT1, hCNT3, and dCK positively contribute to gemcitabine activity and to cancer cells' sensitivity to gemcitabine.…”

Deoxycytidine kinase is overexpressed in poor outcome breast cancer and determines responsiveness to nucleoside analogs

“…Alternatively, A549 cells expressing shRNAs targeting GFP or DCK were seeded for proliferation assays according to the 3T3 protocol in absence of drug or presence of dFdC (10 nM) (right panel). Error bars denote SD of triplicate independent experiments outcome in patients with resected pancreatic cancer who received dFdC as adjuvant therapy [30,32]. Moreover, a recent study reported that the quantitative analysis of DCK mRNA using FFPE tissue samples can be used to predict the sensitivity to gemcitabine-based adjuvant therapy in patients with pancreatic cancer.…”