Cathepsin V is correlated with the prognosis and tumor microenvironment in liver cancer

• Published in: Molecular carcinogenesis 2024-03, Vol.63 (3), p.400-416
• Main Authors: Liu, Junyu, Zhang, Wen, Wang, Zhijie, Wang, Yichuan, Li, Tianxing, Wang, Yaping, Ding, Jin, Ning, Beifang
• Format: Article
• Language: English
• Subjects: Atrophy; Carcinoma, Hepatocellular - genetics; Cathepsins - genetics; CD4 antigen; Cell cycle; Cell Cycle - genetics; Cell Cycle Proteins; Cell proliferation; Correlation analysis; CTSV; DNA microarrays; Gene expression; Gene set enrichment analysis; Genes; Genomes; Hepatocellular carcinoma; Hepatocytes; Humans; Immunohistochemistry; Liver cancer; Liver Neoplasms - genetics; Lymphocytes T; Macrophages; Medical prognosis; Metastases; Prognosis; Regression analysis; Survival analysis; Transcriptomics; Tumor cell lines; Tumor microenvironment; Tumor Microenvironment - genetics
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.23660

Recent studies have shown that high cell cycle activity negatively correlates with antitumor immunity in certain cancer types. However, a similar correlation has not been proven in liver cancer. We downloaded transcriptomic profiles of the cancer genome atlas‐liver hepatocellular carcinoma (TCGA‐LIHC) and assessed the cell cycle distribution of samples using single sample gene set enrichment analysis (ssGSEA), termed the cell cycle score (CCS). We obtained cell cycle‐related differentially expressed prognostic genes and identified CENPA, CDC20, and CTSV using LASSO regression. We studied the effect of CTSV on clinical features and immune alterations in liver cancer based on TCGA‐LIHC data. In vitro and in vivo experiments were performed to validate the role of CTSV in liver cancer using liver cancer cell lines and tissues. We found that the CCS closely correlated with the clinical features and prognosis of patients in TCGA‐LIHC. Analysis of differentially expressed genes (DEGs), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression identified cathepsin V (CTSV) with prognostic significance in LIHC. Importantly, single‐gene survival analysis of CTSV using microarray and sequencing data indicated that high levels of CTSV expression correlated with an unfavorable prognosis in various cancers. Gene set enrichment analysis revealed that high CTSV expression closely correlated with decreased expression of metabolic genes and increased expression of cell cycle genes. Furthermore, difference and correlation analyses of the relationship between CTSV expression and immune infiltrates, determined using CIBERSORT and TIMER algorithms, revealed that CTSV expression correlated with macrophages and CD4+ T cells. In vitro and in vivo experiments revealed that knockdown of CTSV inhibited liver cancer cells proliferation. Immunohistochemical staining showed that high CTSV expression correlated with macrophage infiltration in liver cancer tissues, predicted a poor prognosis, and is associated with the effectiveness of hepatocellular carcinoma treatment. In couclusion, CTSV is a novel cell cycle‐associated gene with clinical significance in HCC.