Identification of TPD52 and DNAJB1 as two novel bile biomarkers for cholangiocarcinoma by iTRAQ‑based quantitative proteomics analysis

• Published in: Oncology reports Vol. 42; no. 6; pp. 2622 - 2634
• Main Authors: Ren, Hongyue, Luo, Mingxu, Chen, Jinzhong, Zhou, Yanming, Li, Xiumei, Zhan, Yanyan, Shen, Dongyan, Chen, Bo
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.12.2019; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Analysis; Bile; Bile - chemistry; Bile Duct Neoplasms - diagnosis; Bile Duct Neoplasms - mortality; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - cytology; Bile Ducts, Intrahepatic - pathology; Biliary tract cancer; Biological markers; Biomarkers; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Cancer; Cancer therapies; Cell culture; Cell Line, Tumor; Cholangiocarcinoma; Cholangiocarcinoma - diagnosis; Cholangiocarcinoma - mortality; Cholangiocarcinoma - pathology; Chromatography, High Pressure Liquid - methods; Computational Biology; Epithelial Cells - pathology; Female; Gallbladder; Gene Expression Profiling; Heat shock proteins; Hospitals; HSP40 Heat-Shock Proteins - analysis; HSP40 Heat-Shock Proteins - metabolism; Humans; Identification; Immunohistochemistry; Male; Medical prognosis; Middle Aged; Neoplasm Proteins - analysis; Neoplasm Proteins - metabolism; Novels; Penicillin; Prognosis; Protein expression; Proteins; Proteomics; Proteomics - methods; Real-Time Polymerase Chain Reaction; Tandem Mass Spectrometry - methods; Tissue Array Analysis; Tumors; Up-Regulation; China
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2019.7387

Cholangiocarcinoma (CCA) represents a type of epithelial cancer with a late diagnosis and poor outcome. However, the molecular mechanisms responsible for the development of CCA have not yet been fully identified. Thus, in this study, we aimed to elucidate some of these mechanisms. For this purpose, isobaric tags for relative and absolute quantification (iTRAQ) was performed to analyze the secretory proteins from the 2 CCA cell lines, TFK1 and HuCCT1, as well as from a normal biliary epithelial cell line, human intrahepatic biliary epithelial cells (HiBECs). Differentially expressed proteins (DEPs) were identified and biological process analysis was performed according to the Gene Ontology (GO) functional classification annotation and KEGG metabolic pathway map analysis. tumor protein D52 (TPD52) and DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) were validated using RT‑qPCR, western blot analysis and immunohistochemistry. In total, 778 proteins were identified as DEPs. Following validation, TPD52 and DNAJB1 were used for further analysis. The expression levels of TPD52 and DNAJB1 were elevated in CCA cell lines, tissues and bile samples, suggesting that these proteins may contribute to tumor pathogenesis. In addition, the expression levels of TPD52 and DNAJB1 were found to be closely associated with the clinical parameters and prognosis of patients with CCA. On the whole, the findings of this study indicate that TPD52 and DNAJB1 may serve as novel bile biomarkers for CCA.