The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma

// Qi Ling 1, 2, * , Xiao Xu 1, 2, * , Panpan Ye 3, * , Haiyang Xie 1, 2 , Feng Gao 1, 2 , Qichao Hu 2 , Zhikun Liu 1, 2 , Xuyong Wei 1, 2 , Christian Röder 4 , Anna Trauzold 4 , Holger Kalthoff 4 , Shusen Zheng 1, 2 1 Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China 2 Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China 3 The Ophthalmology Center, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China 4 Institute for Experimental Cancer Research, Comprehensive Cancer Center North, CAU, Kiel, Germany * These authors contributed equally to this work Correspondence to: Shusen Zheng, email: zyzss@zju.edu.cn Holger Kalthoff, email: hkalthoff@email.uni-kiel.de Keywords: anatomy, microRNA, pancreatic cancer, recurrence Received: January 22, 2016      Accepted: January 10, 2017      Published: January 20, 2017 ABSTRACT Different clinical presentations and prognoses have been implied between pancreatic head and body/tail cancers. We aimed to identify the prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). Thirty-two pairs of patients with strictly matched early stage (II) pancreatic head and body/tail cancers were enrolled. The molecular feature of the two subtypes of PDAC was assessed on the level of miRNA expression. Out of the 64 patients, 34 (53.1%) had tumor recurrence after radical resection during the follow-up period (2.3 ± 0.8 years). Both overall and tumor-free survival were significantly higher in the patients with pancreatic body/tail cancer compared with those with pancreatic head cancer. Patient age and tumor location were the independent prognostic factors for tumor recurrence. A remarkably lower expression of miR-501-3p and higher expression of miR-375 were found and were further verified in pancreatic body/tail cancer tissues compared with pancreatic head cancer tissues. The low expression of miR-501-3p was significantly associated with a low risk of tumor recurrence. Both, subcutaneous and orthotopic PDAC mouse models presented highly invasive tumor phenotypes upon up-regulated miR-501-3p expression. An in vitro study showed that miR-501-3p promoted the invasiveness of PDAC cells possibly via suppressing E-cadherin. In summary, at resectable early stage, pancreatic body/tail cancer presents a less malignant phenotype associated with deregulation of miR-501-3p compared with pancreatic head cancer.