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

• DOI: 10.1593/neo.10458
• Publication Date: 2015-04-23T13:10:02Z
• Authors: Hayato Fujita; Kenoki Ohuchida; Kazuhiro Mizumoto; Soichi Itaba; Tetsuhide Ito; Kohei Nakata; Jun Yu; Tadashi Kayashima; Ryota Souzaki; Tatsuro Tajiri; Tatsuya Manabe; Takao Ohtsuka; Masao Tanaka
• Keywords: Adult; Male; Antimetabolites, Antineoplastic; Biopsy, Fine-Needle; Adenocarcinoma; Deoxycytidine; Equilibrative Nucleoside Transporter 1; Immunoenzyme Techniques; Carcinoma, Adenosquamous; 03 medical and health sciences; 0302 clinical medicine; Cytidine Deaminase; Deoxycytidine Kinase; Biomarkers, Tumor; Humans; RC254-282; Aged; Aged, 80 and over; Gene Expression Profiling; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Middle Aged; 3. Good health; Gene Expression Regulation, Neoplastic; Feasibility Studies; Female

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.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.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 (<2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P = .0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens.Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC.