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. 2009 Jun 16;28(1):83.
doi: 10.1186/1756-9966-28-83.

Gemcitabine sensitivity-related mRNA expression in endoscopic ultrasound-guided fine-needle aspiration biopsy of unresectable pancreatic cancer

Reiko Ashida  1 , Bunzo Nakata, Minoru Shigekawa, Nobumasa Mizuno, Akira Sawaki, Kosei Hirakawa, Tetsuo Arakawa, Kenji Yamao
Affiliations

Gemcitabine sensitivity-related mRNA expression in endoscopic ultrasound-guided fine-needle aspiration biopsy of unresectable pancreatic cancer

Reiko Ashida et al. J Exp Clin Cancer Res. .

Abstract

Background: 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).

Methods: mRNAs 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.

Results: Among 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).

Conclusion: dCK 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.

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Figures

Figure 1
Figure 1
Focused DNA array containing quadruplicate sets of oligonucleotide array sequences for 133 genes. High reproducibility of gene expression is confirmed in corresponding spots of the quadruplicate.
Figure 2
Figure 2
Probability of survival for patients with unresectable pancreatic ductal cancer stratified by gemcitabine efficacy. Open circles, GEM-effective group. Closed circles, GEM-non-effective group. There is a significant difference between survival in the two groups.
Figure 3
Figure 3
Representative electropherogram of total RNA extracted from pancreatic cancer obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy. The ratio of 28S to 18S of ribosomal RNA indicates good quality of total RNA.
See this image and copyright information in PMC

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