Abstract
BackgroundThe aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA).MethodsmRNAs extracted from 35 pancreatic tubular adenocarcinoma tissues obtained by EUS-FNA before GEM-treatment were studied. mRNAs were amplified and applied to a Focused DNA Array, which was restricted to well-known genes, including GEM sensitivity-related genes, deoxycytidine kinase (dCK), human equilibrative nucleoside transporter 1 (hENT1), hENT2, dCMP deaminase, cytidine deaminase, 5'-nucleotidase, ribonucleotide reductase 1 (RRM1) and RRM2. mRNA levels were classified into high and low expression based on a cut-off value defined as the average expression of 35 samples. These 35 patients were divided into the following two groups. Patients with partial response and those with stable disease whose tumor markers decreased by 50% or more were classified as the effective group. The rest of patients were classified as the non-effective group. The relationship between GEM efficacy and mRNA expression was then examined by chi-squared test.ResultsAmong these GEM sensitivity-related genes, dCK alone showed a significant correlation with GEM efficacy. Eight of 12 patients in the effective group had high dCK expression, whereas 16 of 23 patients in non-effective group had low dCK expressions (P = 0.0398).ConclusiondCK mRNA expression is a candidate indicator for GEM efficacy in unresectable pancreatic cancer. Quantitative mRNA measurements of dCK using EUS-FNA samples are necessary for definitive conclusions.
Highlights
The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA)
Clinical outcome Five of 35 patients who completed two courses of GEM monotherapy showed partial response (PR), stable disease (SD) was seen in 19 patients, and progressive disease was seen in 11 patients
Abnormal levels of tumor markers in seven of 17 SD-patients decreased by 50% or more as compared to pretreatment values
Summary
The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). The standard treatment for unresectable pancreatic cancer was previously 5-fluorouracil (5-FU)-based chemotherapy. In 1997, it was reported that gemcitabine (GEM) conferred significantly longer survival and clinical benefits when compared to 5-FU in patients with locally advanced or metastatic pancreatic cancer [1]. Recent investigations using cell lines or surgical specimens have revealed that the expressions of human equilibrative nucleoside transporter 1 (hENT1) [2,3,4] and the GEMmetabolism-related enzymes such as deoxycytidine kinase (dCK) [5,6] are putative predictors for the efficacy of GEM treatment. If GEM could be selectively administered to patients with GEM-sensitive tumors based on the expression of these genes in the tumor, maximum efficacy could be achieved and the unpleasant side effects in GEM-resistant patients may be avoided
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