Gene Expression Levels as Predictive Markers of Outcome in Pancreatic Cancer after Gemcitabine-Based Adjuvant Chemotherapy

• Published in: Neoplasia (New York, N.Y.) N.Y.), 2010-10, Vol.12 (10), p.807,IN7-817,IN8
• Main Authors: Fujita, Hayato, Ohuchida, Kenoki, Mizumoto, Kazuhiro, Itaba, Soichi, Ito, Tetsuhide, Nakata, Kohei, Yu, Jun, Kayashima, Tadashi, Souzaki, Ryota, Tajiri, Tatsuro, Manabe, Tatsuya, Ohtsuka, Takao, Tanaka, Masao
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - therapeutic use; Biomarkers, Tumor - genetics; Biopsy, Fine-Needle; Carcinoma, Adenosquamous - drug therapy; Carcinoma, Adenosquamous - genetics; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Deoxycytidine Kinase - genetics; Deoxycytidine Kinase - metabolism; Equilibrative Nucleoside Transporter 1 - genetics; Equilibrative Nucleoside Transporter 1 - metabolism; Feasibility Studies; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - physiology; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleoside Diphosphate Reductase - genetics; Ribonucleoside Diphosphate Reductase - metabolism; RNA, Messenger - genetics; Survival Rate; Treatment Outcome; Tumor Cells, Cultured; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1593/neo.10458

BACKGROUND AND AIMS: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. MATERIALS AND METHODS: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P = .0067), low RRM2 (P = .003), and high GEM score (P = .0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (