Abstract
Previous studies showed that aberrant CDH1 or/and HDAC3 localization is essential for the progression of some human cancers. Here, we investigate the prognostic significance of aberrant CDH1 and HDAC3 localization in 84 pancreatic cancer patients. Our results show that increases in both membrane and cytoplasmic CDH1 correlate with lymph node metastasis (P = 0.026 and P < 0.001, respectively) and clinical stage (P = 0.020 and P < 0.001, respectively). Increased nuclear HDAC3 correlates with lymph node metastasis (P < 0.001) and advanced clinical stage (P < 0.001), but increased cytoplasmic HDAC3 does not (P > 0.05). Multivariate analysis showed that nuclear HDAC3 and cytoplasmic CDH1 (P = 0.001 and P = 0.010, respectively), as well as tumor differentiation (P = 0.009) are independent prognostic factors. Most importantly, patients with high co-expression of nuclear HDAC3 and cytoplasmic CDH1 had shorter survival times (P < 0.001), more frequent lymph node metastasis (P < 0.001), and advanced clinical stage (P < 0.001). Our studies provide convincing evidence that nuclear HDAC3 and cytoplasmic CDH1 have independent prognostic value in pancreatic cancer and provide novel targets for prognostic therapeutics.
Highlights
Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies, causing the deaths of an estimated 330,400 men and women worldwide in 2012 [1]
Previous studies showed that aberrant CDH1 or/and HDAC3 localization is essential for the progression of some human cancers
Our results show that increases in both membrane and cytoplasmic CDH1 correlate with lymph node metastasis (P = 0.026 and P < 0.001, respectively) and clinical stage (P = 0.020 and P < 0.001, respectively)
Summary
Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies, causing the deaths of an estimated 330,400 men and women worldwide in 2012 [1]. New therapeutic strategies, including therapeutic antibodies or/and small molecule inhibitors, have been successful for a number of malignancies, but results obtained on PC treatments have so far been extremely frustrating [4]. A number of molecular mechanisms responsible for transformation and progression of PC have been identified, providing a set of potential pharmacological targets [5]. Among these is loss of adhesion between tumor cells caused by downregulation of CDH1 ( called E-cadherin) in response to genetic or epigenetic changes [6,7,8]
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