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TMED9 is a poor prognosis marker in hepatocellular carcinoma patients that modulates oncogene trafficking and promote tumorigenesis
Author(s) -
Yang YiChieh,
Lai TsungChing,
Hsiao Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.37
Subject(s) - hepatocellular carcinoma , carcinogenesis , immunohistochemistry , biomarker , oncogene , cancer research , medicine , cancer , oncology , pathology , bioinformatics , biology , cell cycle , biochemistry
Purpose Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related deaths in the world. Due to difficulty of early diagnosis and the treatment in HCC, the prognosis for patients remains poor in the past decade. Therefore, our aim in this study is to establish the screening model to discover novel diagnostic and prognostic markers in HCC patients. Design Systemic analysis of global gene expressions by using Mass Spectrometry is an attractive approach to identify novel biomarkers for the development of therapeutics and diagnostics. In this study, the fresh protein lysates from paired N/T HCC tissues were analyzed by SDS‐PAGE protein MS/MS and tissue MALDI imaging analysis to identify the putative biomarkers. On the other hand, the frozen sections were applied to MALDI imaging MS system and analyzed by Fleximage and ClinPro software. Selected biomarker signatures were evaluated by the available online databases and immunohistochemistry staining was used to stain N/T paired clinical hepatoma tissue array (n=120) for prognostic value analysis. Immunoprecipitation‐MASS was further used to find the identified marker TMED9 binding proteins. Results According to the protein ID analysis, 27 proteins were revealed with more than 1.3 fold of T/N ratio. We further validated these genes by TCGA and GEO databases, which recruited the progression data and the paired N/T sample analysis in their cohort. Among these proteins, we found the importance of the TMED9 in HCC progression. The higher TMED9 mRNA and protein levels were significantly observed in the HCC patients. In addition, the patients who had higher TMED9 accompanied with poor prognosis in our Taiwan cohort. Mechanically, the dyregulation of TMED9 in HCC cells altered the trafficking of targeting proteins from ER to Golgi and may also changes their folding, maturation, and post‐translational modifications to modulate their protein functions or stability. The alteration of TMED9 expression changes the metabolism of functional proteins and promotes the tumorigenecity of HCC. Conclusion Our work not only identified the new protein biomarkers in predicting HCC prognosis, but also showed dyregulation of protein trafficking system could promote HCC progression. These new findings may provide new targets for therapeutic intervention in treating patients with HCC. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .