Aberrant expression of nuclear HDAC3 and cytoplasmic CDH1 predict a poor prognosis for patients with pancreatic cancer

// Feng Jiao 1, 2 * , Hai Hu 1 * , Ting Han 1, 2 * , Meng Zhuo 1 * , Cuncun Yuan 3 , Haiyan Yang 1 , Lei Wang 1, 2 , Liwei Wang 1, 2 1 Department of Medical Oncology and Pancreatic Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China 2 Shanghai Key Laboratory of Pancreatic Diseases, Shanghai 201620, China 3 Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China * These authors are contributed equally to this work Correspondence to: Feng Jiao, e-mail: jiao_f@outlook.com Lei Wang, e-mail: wang_lei744@hotmail.com Liwei Wang, e-mail: yzwlw@hotmail.com Keywords: pancreatic cancer, histone deacetylases 3, CDH1, subcellular localization, prognosis Received: January 05, 2016 Accepted: February 11, 2016 Published: February 24, 2016 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.