Targeted Proteins Reveal Cathepsin D as a Novel Biomarker in Differentiating Hepatocellular Carcinoma from Cirrhosis and Other Liver Cancers
Issued Date
2022-01-01
Resource Type
ISSN
15137368
eISSN
2476762X
Scopus ID
2-s2.0-85133105934
Pubmed ID
35763644
Journal Title
Asian Pacific Journal of Cancer Prevention
Volume
23
Issue
6
Start Page
2017
End Page
2025
Rights Holder(s)
SCOPUS
Bibliographic Citation
Asian Pacific Journal of Cancer Prevention Vol.23 No.6 (2022) , 2017-2025
Suggested Citation
Chuaypen N., Sriphoosanaphan S., Vorasittha A., Pinjaroen N., Thongboonkerd V., Tangkijvanich P., Sirichindakul P. Targeted Proteins Reveal Cathepsin D as a Novel Biomarker in Differentiating Hepatocellular Carcinoma from Cirrhosis and Other Liver Cancers. Asian Pacific Journal of Cancer Prevention Vol.23 No.6 (2022) , 2017-2025. 2025. doi:10.31557/APJCP.2022.23.6.2017 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86344
Title
Targeted Proteins Reveal Cathepsin D as a Novel Biomarker in Differentiating Hepatocellular Carcinoma from Cirrhosis and Other Liver Cancers
Author's Affiliation
Other Contributor(s)
Abstract
Objective: Hepatocellular carcinoma (HCC) represents a global health concern, particularly in Southeast Asia where hepatitis B virus (HBV) infection is common. In this study, we applied tissue-based proteomics to identify novel serological proteins for HCC and validated their performance in serum specimens. Methods: In a discovery set, liver tissue specimens of HBV-related HCC, intrahepatic cholangiocarcinoma (iCCA) and colorectal cancer with liver metastasis (CRLM) were analyzed using mass spectrometry (LTQ-Orbitrap-XL). A subset of proteins that showed highly expressed in HCC were then confirmed by Western blotting. Additionally, clinical significance of selected candidate proteins was tested in serum samples of 80 patients with HBV-related HCC, 50 patients with HBV-related liver cirrhosis and 30 healthy controls. Results: Based on LTQ-Orbitrap-XL mass spectrometer, various differentially expressed proteins (DEPs) between tumor and adjacent non-tumor tissues were identified. These included 77 DEPs for HCC, 77 DEPs for iCCA and 55 DEPs for CRLM. Among selected candidate proteins, annexin A2 and cathepsin D were confirmed to be overexpressed in HCC tissue by Western blot analysis. In a validate cohort, serum cathepsin D level, but not annexin A2, was significantly higher in HCC compared with the non-HCC groups. Serum cathepsin D level was also positively correlated with tumor size and tumor stage. Additionally, the combined assay of serum cathepsin D and alpha-fetoprotein had a high sensitivity in detecting early HCC (83%) and intermediate/advanced HCC (96%). Moreover, patients with low serum cathepsin D (<305 ng/mL) displayed significantly better overall survival than those whose serum levels were high (≥305 ng/mL). Conclusions: Proteomics and subsequent validation revealed cathepsin D as a novel biomarker for HCC. Apart from its diagnostic role, serum cathepsin D might also serve as a prognostic biomarker of HCC. Additional large-scale studies are needed to verify our findings