Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer

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• 作者：Yukihiko Hiroshima MD (1)
  Fumio Nakamura MD ; PhD (2)
  Hiroshi Miyamoto MD (1)
  Ryutaro Mori MD ; PhD (1)
  Koichi Taniguchi MD ; PhD (1)
  Ryusei Matsuyama MD ; PhD (1)
  Hirotoshi Akiyama MD ; PhD (1)
  Kuniya Tanaka MD ; PhD (1)
  Yasushi Ichikawa MD ; PhD (1) (3)
  Shingo Kato MD (4)
  Noritoshi Kobayashi MD ; PhD (4)
  Kensuke Kubota MD ; PhD (4)
  Yoji Nagashima MD ; PhD (5) (6)
  Yoshio Goshima MD ; PhD (2)
  Itaru Endo MD ; PhD (1)
  
• 刊名：Annals of Surgical Oncology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：20
• 期：3-supp
• 页码：369-378
• 全文大小：757 KB
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• 作者单位：Yukihiko Hiroshima MD (1)
  Fumio Nakamura MD, PhD (2)
  Hiroshi Miyamoto MD (1)
  Ryutaro Mori MD, PhD (1)
  Koichi Taniguchi MD, PhD (1)
  Ryusei Matsuyama MD, PhD (1)
  Hirotoshi Akiyama MD, PhD (1)
  Kuniya Tanaka MD, PhD (1)
  Yasushi Ichikawa MD, PhD (1) (3)
  Shingo Kato MD (4)
  Noritoshi Kobayashi MD, PhD (4)
  Kensuke Kubota MD, PhD (4)
  Yoji Nagashima MD, PhD (5) (6)
  Yoshio Goshima MD, PhD (2)
  Itaru Endo MD, PhD (1)
  
  1. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  2. Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  3. Department of Clinical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  4. Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  5. Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  6. Advanced Medical Research Center, Yokohama City University, Yokohama, Japan
  
• ISSN：1534-4681

文摘

Background Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer. Methods Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n?=?53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors. Results Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p?=?0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2?%) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p?=?0.044), stage (p?=?0.019), and liver metastasis (p?=?0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival. Conclusions Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer.