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

Qi Ling,Xiao Xu,Xuyong Wei,Shusen Zheng,Holger Kalthoff,Zhikun Liu,Christian Röder,Feng Gao,Anna Trauzold,Panpan Ye,Qichao Hu,Haiyang Xie

doi:10.18632/oncotarget.14768

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.

Highlights

The tumor-node-metastasis (TNM) system has been widely used to stage tumors, predict prognosis and develop a therapeutic strategy
Both overall survival and tumor-free survival were significantly higher in the patients with pancreatic body/tail cancer than in those with pancreatic head cancer (Figure 1A)
The patients with early stage pancreatic body/tail cancer showed increased survival compared with the paired patients with pancreatic head cancer, which is consistent with a previous report [9]

Summary

Introduction

The tumor-node-metastasis (TNM) system has been widely used to stage tumors, predict prognosis and develop a therapeutic strategy. With regard to the pancreas, tumor localization to the head has been found to be independently associated with local invasiveness and recurrence in pancreatic serous cystic neoplasms and intraductal papillary mucinous neoplasms [2, 3]. Insulinpositive endocrine cells, which are present at a greater concentration in the tail of the pancreas compared with the www.impactjournals.com/oncotarget head, could serve as a cell-of-origin of pancreatic ductal adenocarcinoma (PDAC) following oncogenic mutation inducement and pancreatic injury [5]. These findings indicate that the head, body, and tail of the pancreas may have different malignant potentials. Early-stage tumors in the pancreas head may be associated with lower survival compared with those in the pancreas body/tail [6]

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Conclusion