Ann Surg Oncol (2011) 18:2381–2387 DOI 10.1245/s10434-011-1602-x O R I G I N A L A R T I C L E – T R A N S L A T I O N A L R E S E A R C H A N D B I O M A R K E R S MicroRNA Expression as a Predictive Marker for Gemcitabine Response after Surgical Resection of Pancreatic Cancer Kenoki Ohuchida, PhD1,2, Kazuhiro Mizumoto, PhD1,3, Tadashi Kayashima, MD1, Hayato Fujita, PhD1, Taiki Moriyama, PhD1, Takao Ohtsuka, PhD1, Junji Ueda, PhD1, Eishi Nagai, PhD1, Makoto Hashizume, PhD2, and Masao Tanaka, PhD1 1Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 2Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 3Kyushu University Hospital Cancer Center, Fukuoka, Japan ABSTRACT Background. 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. Methods. 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 sam- ples obtained from 90 patients with or without gemcitabine treatment after resection of pancreatic cancer. Results. We identiﬁed 24 microRNAs whose expression was altered in gemcitabine-resistant cells. qRT-PCR anal- yses 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). The Author(s) 2011. This article is published with open access at Springerlink.com First Received: 18 November 2010; Published Online: 23 February 2011 K. Ohuchida, PhD e-mail: kenoki@surg1.med.kyushu-u.ac.jp K. Mizumoto, PhD e-mail: mizumoto@med.kyushu-u.ac.jp Conclusions. miR-142-5p is a promising predictive mar- ker for gemcitabine response in patients with resected pancreatic cancer. Pancreatic cancer is the fourth most common cause of tumor-related death in the industrialized world.1,2 Only 10–20% of pancreatic cancer patients are candidates for surgery at the time of presentation, and fewer than 20% of patients who undergo curative resection are alive after 5 years.3,4 A few recent reports have described the successful use of adjuvant chemotherapies such as 5-ﬂuo- rouracil and gemcitabine.5,6 However, not all patients beneﬁt from such adjuvant chemotherapy, and we cannot predict which patients will beneﬁt most from this treat- ment. Therefore, to improve the prognosis of patients with resected pancreatic cancer, we need to identify speciﬁc markers that can predict responses to adjuvant therapy. Such a personalized therapy, based on the predictive markers, may provide the most appropriate and efﬁcient treatment for a speciﬁc subset of patients. Gemcitabine is a deoxycytidine analog with antitumor activity that bears a resemblance, both structurally and metabolically, to arabinosyl cytosine.7 Gemcitabine is widely accepted as the ﬁrst-line treatment for patients with advanced or resected pancreatic cancer.6,8 However, recent reports showed that the complete plus partial response rate and the disease control rate in advanced pancreatic cancer are 8.0–13.5% and 49.2–62.1%, respectively, even with combination-treatment arms.9,10 The data suggest that approximately half of patients with resected pancreatic cancer do not beneﬁt from gemcitabine-based combination therapies. Therefore, predictive markers are needed to select those patients who may beneﬁt most from gemcita- bine-based therapy. So far, research into the mechanism of