Research Papers:
The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma
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Abstract
Qi Ling1,2,*, Xiao Xu1,2,*, Panpan Ye3,*, Haiyang Xie1,2, Feng Gao1,2, Qichao Hu2, Zhikun Liu1,2, Xuyong Wei1,2, Christian Röder4, Anna Trauzold4, Holger Kalthoff4, Shusen Zheng1,2
1Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
2Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
3The Ophthalmology Center, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
4Institute for Experimental Cancer Research, Comprehensive Cancer Center North, CAU, Kiel, Germany
*These authors contributed equally to this work
Correspondence to:
Shusen Zheng, email: [email protected]
Holger Kalthoff, email: [email protected]
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.
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