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


CONCLUSIONS
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.
Ashida
Reiko
R
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. rashida@uci.edu
Nakata
Bunzo
B
Shigekawa
Minoru
M
Mizuno
Nobumasa
N
Sawaki
Akira
A
Hirakawa
Kosei
K
Arakawa
Tetsuo
T
Yamao
Kenji
K
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D044963:Biopsy, Fine-Needle; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D014463:Ultrasonography; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D000093542:Gemcitabine