Significance of S100P as a biomarker in diagnosis,prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma |
| |
| Authors: | Zhiliang Wu Thidarut Boonmars Isao Nagano Sirintip Boonjaraspinyo Piyarat Srinontong Panaratana Ratasuwan Khuntikeo Narong Phuangphaka Sadee Nielsen Yoichi Maekawa |
| |
| Affiliation: | 1. Department of Parasitology and Infectious Diseases, Gifu University Graduate School of Medicine, Japan;2. Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;3. Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;4. Department of Community Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;5. Department of Anesthesiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;6. Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;7. Division of Clinical Immunology, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand |
| |
| Abstract: | Cholangiocarcinoma (CCA) is a malignancy of bile duct with the difficulty in early diagnosis, poor prognosis and less alternation in therapy. S100P is a member of S100 family proteins and plays important roles in cancers. We investigated the S100P expression and its correlation with clinicopathology in 78 cases of opisthorchiasis‐associated CCA, and the effects of S100P knockdown with shRNA interference on the proliferation, cell cycle, migration, apoptosis and sensitivity to anti‐cancer drug. Extremely high expression of S100P mRNA was detected in the CCA tumor tissues. The increased S100P protein expression was immunohistochemically confirmed and localized in the CCA cytoplasm and/or nuclei as well as in the hyperneoplasia and dysplasia bile ducts, but not in normal bile ducts. The intensity of immunostaining was correlated with survival, tumor stage and metastasis, and the high expression could be an independent prognostic factor. High levels of S100P were detected in the serum and bile fluid of CCA patients. The shRNA‐mediated knockdown of S100P expression inhibited the proliferation in vitro and in vivo, and migration of CCA cells, arrested cell cycle with the up‐regulated expression of cell cycle arrest related factors, p21, p27, GADD45A, and 14‐3‐3 zeta. S100P knockdown also promoted CCA cell apoptosis by up‐regulating expression of apoptosis related factors, DR5, TRADD, caspase 3 and BAX, and increased the sensitivity of CCA cells to the chemotherapeutic agents sunitinib and apigenin. Taken together, this study indicates that S100P might be a promising biomarker for the diagnosis, prognosis and therapy of CCA. |
| |
| Keywords: | cholangiocarcinoma S100P biomarker shRNA |
|
|
