- 作者: Yi-Chieh Yang, Ming-Hsien Chien, Tsung-Ching Lai, Min-Che Tung, Yi-Hua Jan, Wei-Ming Chang, Shih-Ming Jung, Ming-Huang Chen, Chun-Nan Yeh and Michael Hsiao
- 作者服務機構: 1.Department of Medical Research, Tungs’ Taichung Metro Harbor Hospital, Taichung, Taiwan 2.Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan 3.Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan 4.Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 5.Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan 6.TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan 7.Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 8.Department of Medical Research, Tungs’ Taichung Metro Harbor Hospital, Taichung, Taiwan 9.School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 10.Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 11.Department of Oncology, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, 112, Taiwan 12.School of Medicine, National Yang-Ming University, Taipei, Taiwan 13.Department of General Surgery and Liver Research Center, Linkou Branch, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, 333, Taiwan 14.Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan 15.Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
Background
Due to the difficulties in early diagnosing and treating hepatocellular carcinoma (HCC), prognoses for patients remained poor in the past decade. In this study, we established a screening model to discover novel prognostic biomarkers in HCC patients.
Methods
Candidate biomarkers were screened by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analyses of five HCC normal (N)/tumor (T) paired tissues and preliminarily verified them through several in silico database analyses. Expression levels and functional roles of candidate biomarkers were respectively evaluated by immunohistochemical staining in N/T paired tissue (n = 120) and MTS, colony formation, and transwell migration/invasion assays in HCC cell lines. Associations of clinicopathological features and prognoses with candidate biomarkers in HCC patients were analyzed from GEO and TCGA datasets and our recruited cohort.
Results
We found that the transmembrane P24 trafficking protein 9 (TMED9) protein was elevated in HCC tissues according to a global proteomic analysis. Higher messenger (m)RNA and protein levels of TMED9 were observed in HCC tissues compared to normal liver tissues or pre-neoplastic lesions. The TMED9 mRNA expression level was significantly associated with an advanced stage and a poor prognosis of overall survival (OS, p = 0.00084) in HCC patients. Moreover, the TMED9 protein expression level was positively correlated with vascular invasion (p = 0.026), OS (p = 0.044), and disease-free survival (p = 0.015) in our recruited Taiwanese cohort. In vitro, manipulation of TMED9 expression in HCC cells significantly affected cell migratory, invasive, proliferative, and colony-forming abilities.
Conclusions
Ours is the first work to identify an oncogenic role of TMED9 in HCC cells and may provide insights into the application of TMED9 as a novel predictor of clinical outcomes and a potential therapeutic target in patients with HCC. - 中文關鍵字:
- 英文關鍵字: Hepatocellular carcinoma, Mass spectrometric imaging, Transmembrane P24 trafcking protein 9, Vascular invasion, Prognosis