title: iTRAQ-2DLC-ESI-MS/MS based identification of a new set of immunohistochemical biomarkers for classification of dysplastic nodules and small hepatocellular carcinoma.
abstract: The study aims to develop novel clinical immunohistochemical biomarkers for distinguishing small hepatocellular carcinoma (sHCC) from dysplastic nodules (DN). iTRAQ-2DLC-ESI-MS/MS technique was used to screen immunohistochemical biomarkers between precancerous lesions (liver cirrhosis and DN) and sHCC. A total of 1951 proteins were quantified, including 52 proteins upregulated in sHCC and 95 proteins downregulated in sHCC by at least 1.25- or 0.8-fold at p < 0.05. The selected biomarker candidates were further verified using Western blotting and immunohistochemistry. Furthermore, receiver operation characteristics (ROC) curves and logistic regression model were carried out to evaluate the diagnostic values of the biomarkers. Finally, aminoacylase-1 (ACY1) and sequestosome-1 (SQSTM1) were chosen as novel candidate biomarkers for distinction of sHCC from DN. A constructed logistic regression model included ACY1, SQSTM1, and CD34. The sensitivity and specificity of this model for distinguishing sHCC from DN was 96.1% and 96.7%. In conclusion, ACY1 and SQSTM1 were identified as novel immunohistochemical biomarkers distinguishing sHCC from DN. In conclusion, expression levels of CD34, ACY1, and SQSTM1 can be used to establish an accurate diagnostic model for distinction of sHCC from DN.
authors.affiliation: Liver Cancer Institute, Zhong Shan Hospital and §Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Cong
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Hong
authors.initials: H
authors.lastname: Shu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liu
authors.forename: Guo-Quan
authors.initials: GQ
authors.lastname: Yan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Kang
authors.forename: Kun
authors.initials: K
authors.lastname: Guo
authors.forename: Zhe-Dong
authors.initials: ZD
authors.lastname: Wang
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Yang
authors.forename: Yin-Kun
authors.initials: YK
authors.lastname: Liu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor