Proteomics-based identification of TMED9 is linked to vascular invasion and poor prognoses in patients with hepatocellular carcinoma

Journal of Biomedical Science

Chun-Nan Yeh¹  Min-Che Tung²  Yi-Chieh Yang³  Ming-Huang Chen⁴  Shih-Ming Jung⁵  Yi-Hua Jan⁶  Michael Hsiao⁷  Tsung-Ching Lai⁸  Wei-Ming Chang⁹  Ming-Hsien Chien^1,10 

[1] Department of General Surgery and Liver Research Center, Linkou Branch, Chang Gung Memorial Hospital, Chang Gung University, 333, Taoyuan, Taiwan;Department of Medical Research, Tungs’ Taichung Metro Harbor Hospital, Taichung, Taiwan;Department of Medical Research, Tungs’ Taichung Metro Harbor Hospital, Taichung, Taiwan;Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 11031, Taipei, Taiwan;Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, 11529, Nankang, Taipei, Taiwan;Department of Oncology, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, 112, Taipei, Taiwan;School of Medicine, National Yang-Ming University, Taipei, Taiwan;Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan;Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, 11529, Nankang, Taipei, Taiwan;Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, 11529, Nankang, Taipei, Taiwan;Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan;Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, 11529, Nankang, Taipei, Taiwan;Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, 11529, Nankang, Taipei, Taiwan;School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan;Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 11031, Taipei, Taiwan;Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan;TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan;

关键词: Hepatocellular carcinoma;    Mass spectrometric imaging;    Transmembrane P24 trafficking protein 9;    Vascular invasion;    Prognosis;   

DOI  :  10.1186/s12929-021-00727-5

来源: Springer

【 摘 要 】

BackgroundDue 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.MethodsCandidate 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.ResultsWe 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.ConclusionsOurs 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.

【 授权许可】

CC BY