MicroRNA Expression as a Predictive Marker for Gemcitabine Response after Surgical Resection of Pancreatic Cancer

• DOI: 10.1245/s10434-011-1602-x
• Publication Date: 2011-02-22T14:01:54Z
• Authors: Kenoki Ohuchida; Kazuhiro Mizumoto; Tadashi Kayashima; Hayato Fujita; Taiki Moriyama; Takao Ohtsuka; Junji Ueda; Eishi Nagai; Makoto Hashizume; Masao Tanaka
• Keywords: Adult; Aged, 80 and over; Male; Antimetabolites, Antineoplastic; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; Middle Aged; Prognosis; Combined Modality Therapy; Deoxycytidine; 3. Good health; Pancreatic Neoplasms; Survival Rate; MicroRNAs; Oncology; Biomarkers, Tumor; Humans; Surgery; Translational Research and Biomarkers; Female; RNA, Messenger; Aged; Carcinoma, Pancreatic Ductal; Oligonucleotide Array Sequence Analysis

To improve the prognosis of patients after resection of pancreatic cancer, the most appropriate and efficient treatment should be provided to specific subsets of patients. Our aim was to identify promising microRNAs as markers to predict responses to gemcitabine in patients with resected pancreatic cancer.Two gemcitabine-resistant pancreatic cancer cell lines were established, and global microRNA expression analyses was performed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Eleven miRNAs were selected as putative predictive markers and analyzed by means of macrodissected formalin-fixed, paraffin-embedded samples obtained from 90 patients with or without gemcitabine treatment after resection of pancreatic cancer.We identified 24 microRNAs whose expression was altered in gemcitabine-resistant cells. qRT-PCR analyses showed that patients with high miR-142-5p and miR-204 expression had significantly longer survival times than those with low miR-142-5p (P = 0.0077) and miR-204 (P = 0.0054) expression in the gemcitabine-treated group. This was not seen in the nontreated group. Multivariate analyses showed that miR-142-5p expression was an independent prognostic marker only in patients treated with gemcitabine (P = 0.034).miR-142-5p is a promising predictive marker for gemcitabine response in patients with resected pancreatic cancer.