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Tandem Mass Tag-Based Proteomic Analysis of Potential Biomarkers for Hepatocellular Carcinoma Differentiation

Authors Wang W, Li Q, Huang G, Lin BY, Lin D, Ma Y, Zhang Z, Chen T, Zhou J

Received 4 August 2020

Accepted for publication 28 January 2021

Published 12 February 2021 Volume 2021:14 Pages 1007—1020

DOI https://doi.org/10.2147/OTT.S273823

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Sanjay Singh


Wei Wang,1,* Qiang Li,2,* Ge Huang,3 Bing-yao Lin,1 Dongzi Lin,1 Yan Ma,1 Zhao Zhang,4 Tao Chen,1 Jie Zhou1

1Department of Laboratory, Foshan Fourth People’s Hospital, Foshan, 528000, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510000, People’s Republic of China; 3Intensive Care Unit, Foshan Fourth People’s Hospital, Foshan, 528000, People’s Republic of China; 4Research and Development Centre, South China Institute of Biomedicine, Guangdonglongsee Biomedical Co., Ltd, Guangzhou, 510000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhao Zhang
Research and Development Centre, South China Institute of© Biomedicine, Guangdonglongsee Biomedical Co., Ltd, 5/F Building A, No. 83 Ruihe Road, Huangpu District, Guangzhou, 510535, People’s Republic of China
Email zhangzhao0402@163.com
Ge Huang
Intensive Care Unit, Foshan Fourth People’s Hospital, No. 106, Jinlan Road, Foshan, 528000, People’s Republic of China
Email Lang.x.c.d@sina.com

Purpose: The poor prognosis of hepatocellular carcinoma (HCC) urgent us to discover early and effective biomarkers. In this study, we applied tandem mass tag (TMT)-based proteomic analysis to discover potential protein markers for HCC identification and differentiation.
Patients and Methods: Fifteen patients, well-differentiated (G1, N = 5), moderate-differentiated (G2, N = 5), and poorly differentiated (G3, N = 5), with 30 matched pair tissues (both tumor and adjacent non-tumor tissues derived from the same patient) were enrolled. All samples were subjected to TMT labeling and LC−MS/MS analysis. The identified proteins were subsequently assigned to GO and KEGG for predicting function. The identified protein candidates were validated using immunohistochemistry (IHC).
Results: A total of 1010 proteins were identified. Of these, 154 differentially expressed proteins (DEPs), 100 up-regulated and 54 down-regulated, were found between tumor and adjacent non-tumor tissues; 12 DEPs, 9 up-regulated and 3 down-regulated, were found between G1 and G3 tissues; 8 DEPs, 5 up-regulated and 3 down-regulated, were found between G1 and G2 tissues; 11 DEPs, 8 up-regulated and 3 down-regulated, were found between G2 and G3 tissues. Among them, ASS1 and CPS1 were significantly up-regulated while UROD and HBB were significantly down-regulated in G3 compared with G1 and G2 tumors. Three proteins, CYB5A, FKBP11 and YBX1, were significantly up-regulated in G1 compared with both G2 and G3 tumors. The 7 biomarker candidates were further verified by IHC.
Conclusion: A variety of DEPs related to the histological differentiation of HCC were identified, among which ASS1, CPS1, URPD and HBB proteins were potential biomarkers for distinguishing poorly differentiated HCC, while CYB5A, FKBP11 and YBX1 were potential biomarkers for distinguishing well-differentiated HCC. Our findings may further provide a new insight facilitating the diagnosis and prognosis of HCC.

Keywords: tandem mass tag, proteomic analysis, hepatocellular carcinoma, histological differentiation, diagnosis, prognosis

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