The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma.
The prognostic relevance of primary tumor location in patients undergoing resection for pancreatic ductal adenocarcinoma.
复制标题
DOI：
10.18632/oncotarget.14768
复制
发表时间：
2017-02-28
期刊：
影响因子：
--
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Ling Q;Xu X;Ye P;Xie H;Gao F;Hu Q;Liu Z;Wei X;Röder C;Trauzold A;Kalthoff H;Zheng S
胰头癌和体/尾癌的临床表现和预后不同。我们的目的是确定胰腺导管腺癌（PDAC）切除术患者原发肿瘤位置的预后相关性。入选了32对具有严格匹配的早期（II）胰腺头和体/尾癌的患者。在miRNA表达水平上评估PDAC的两种亚型的分子特征。在64例患者中，34例（53.1%）在根治性切除术后随访期间（2.3 ± 0.8年）肿瘤复发。与胰头癌患者相比，胰体尾癌患者的总体生存率和无瘤生存率均显著较高。患者年龄和肿瘤部位是肿瘤复发的独立预后因素。与胰头癌组织相比，胰腺体尾癌组织中miR-501- 3 p的表达显著降低，miR-375的表达显著升高，并进一步证实了这一点。miR-501- 3 p的低表达与肿瘤复发的低风险显著相关。在上调miR-501- 3 p表达后，皮下和原位PDAC小鼠模型均呈现高度侵袭性肿瘤表型。体外研究显示miR-501- 3 p可能通过抑制E-cadherin而促进PDAC细胞的侵袭力。总之，在可切除的早期阶段，与胰头癌相比，胰体/尾癌呈现出与miR-501- 3 p失调相关的恶性程度较低的表型。
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.