The Prognostic Significance of CTSV Expression in Patients with Hepatocellular Carcinoma

Yuping He,1,2,&ast; Minghao Xu,2,3,&ast; Chenhao Zhou,2,3 Qiongzhu Dong,2,4 Zhiqiu Hu,2,4,5 Ning Ren2– 4 1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 2Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, People’s Republic of China; 3Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China; 4Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Ren, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China, Tel +86 21 64041990, Email [email protected] Zhiqiu Hu, Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, 170 Xinsong Road, Shanghai, 201199, People’s Republic of China, Tel +86 21 64923400, Email [email protected]: Cathepsin V (CTSV) is a cysteine protease peptidase, which is typically upregulated in cancer and is associated with various oncogenic processes, such as angiogenesis, proliferation, apoptosis, and invasion. The study explored the role of CTSV in hepatocellular carcinoma (HCC) and its potential as a potential biomarker.Patients and Methods: This study collected tumor and peritumoral archived specimens from 180 HCC patients who underwent surgical resection at Zhongshan Hospital, Fudan University (Shanghai, China) between 2009 and 2010. We extracted data from the TCGA and GEO databases and conducted differential expression analysis, univariate Cox regression, and Kaplan-Meier analysis. Ultimately, we determined that CTSV may emerge as a potential biomarker. Then, immunohistochemical staining for CTSV was performed on tumors and adjacent tissues of HCC patients, and a Cox proportional hazards model was constructed to evaluate the prognostic significance of CTSV expression levels. Applied functional enrichment analysis to reveal the underlying molecular mechanisms. Utilized ssGSEA enrichment analysis and TIMER2.0 algorithm to explore the correlation between CTSV expression and immune cells in HCC. In vitro and in vivo experiments were conducted using human liver cancer cell lines to further validate the clinical application value of CTSV.Results: In this study, we observed that CTSV expression was notably elevated in HCC (P < 0.001), and identified a significant association between elevated CTSV expression and reduced overall survival rates in patients. In vitro and in vivo experiments indicated that CTSV knockdown could significantly inhibit the proliferation, migration, and invasion of liver cancer cells, and it was found that the combination of CTSV knockdown with PD-1 inhibitors might enhance the therapeutic effect of PD-1 inhibitors in HCC.Conclusion: CTSV serves as a standalone negative prognostic indicator and possesses clinical significance in HCC.Keywords: Cathepsin V, HCC, biomarker, immune infiltrating cells, PD-1 inhibitor