Citation: SHENG Xiang-Ying, LU Hao-Jie. Differential Proteome Analysis of Hepatitis B Virus-related Hepatocellular Carcinoma with and without Cirrhosis from Formalin-fixed and Paraffin-embedded Tissue Samples[J]. Chinese Journal of Analytical Chemistry, ;2021, 49(9): 1478-1487. doi: 10.19756/j.issn.0253-3820.210441 shu

Differential Proteome Analysis of Hepatitis B Virus-related Hepatocellular Carcinoma with and without Cirrhosis from Formalin-fixed and Paraffin-embedded Tissue Samples

SHENG Xiang-Ying ¹ ,
LU Hao-Jie ^1,2,,

1.
Department of Chemistry, Fudan University, Shanghai 200433, China;
2.
Institutes of Biomedical Sciences and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai 200433, China

Corresponding author: LU Hao-Jie, luhaojie@fudan.edu.cn
Received Date: 18 April 2021
Revised Date: 31 May 2021

Fund Project: Supported by the National Key Research and Development Program of China (No.2016YFA0501300) and the National Natural Science Foundation of China (No.21974025).

Hepatocellular carcinoma (HCC) is the fourth leading cause of deaths among malignancies, of which 30% is caused by hepatitis B virus (HBV). Most of HCC patients are associated with cirrhosis, while 20% occurs in non-cirrhotic liver. Between HBV-related HCC patients with cirrhosis (C-HBV-HCC) and without cirrhosis (NC-HBV-HCC), the mechanism of HCC is different and not yet clear. This study performed differential proteome analysis of NC-HBV-HCC and C-HBV-HCC from formalin-fixed and paraffin-embedded (FFPE) samples, using LC-MS/MS coupled with label-free quantitation. A total of 4083 proteins were identified, and 283 of them were differentially expressed between these two groups. Six proteins were validated by immunohistochemistry, among which HSD17B13/SOD3/CXCL12 were up-regulated in NC-HBV-HCC group, while the expression level of GPD2/CRTAP/CD276 were higher in C-HBV-HCC group. Overall, 6 proteins were validated as biomarker candidates for guiding mechanism research of HBV-related HCC patients with and without cirrhosis, showing the potential to assist clinical management of these two patient types. Bioinformatic analyses showed that cholesterol homeostasis and adipogenesis pathways were upregulated in NC-HBV-HCC compared with C-HBV-HCC, and the 6 biomarker candidates suggested that PI3K/Akt/MMPs and Wnt/β-catenin pathways might be associated with different cancer progresses in NC-HBV-HCC and C-HBV-HCC, providing data and new ideas for the exploration of the tumorigenesis of HBV-related HCC with and without cirrhosis.
- Formalin-fixed and paraffin-embedded,
- Differential proteome,
- Non-cirrhotic liver,
- Cirrhotic liver,
- Hepatitis B virus,
- Hepatocellular carcinoma,
- Biomarker
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