Abstract
Cathepsin A (CTSA) is a lysosomal protease that regulates galactoside metabolism. The previous study has shown CTSA is abnormally expressed in various types of cancer. However, rarely the previous study has addressed the role of CTSA in hepatocellular carcinoma (HCC) and its prognostic value. To study the clinical value and potential function of CTSA in HCC, datasets from the Cancer Genome Atlas (TCGA) database and a 136 HCC patient cohort were analyzed. CTSA expression was found to be significantly higher in HCC patients compared with normal liver tissues, which was supported by immunohistochemistry (IHC) validation. Both gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that CTSA co-expressed genes were involved in ATP hydrolysis coupled proton transport, carbohydrate metabolic process, lysosome organization, oxidative phosphorylation, other glycan degradation, etc. Survival analysis showed a significant reduction both in overall survival (OS) and recurrence-free survival (RFS) of patients with high CTSA expression from both the TCGA HCC cohort and 136 patients with the HCC cohort. Furthermore, CTSA overexpression has diagnostic value in distinguishing between HCC and normal liver tissue [Area under curve (AUC) = 0.864]. Moreover, Gene set enrichment analysis (GSEA) showed that CTSA expression correlated with the oxidative phosphorylation, proteasome, and lysosome, etc. in HCC tissues. These findings demonstrate that CTSA may as a potential diagnostic and prognostic biomarker in HCC.
Highlights
Hepatocellular carcinoma (HCC) has a high mortality rate and is one of the cancers in which incidence gradually increased in recent y ears[1,2]
The gene expression profiling interactive analysis (GEPIA), The Cancer Genome Atlas (TCGA), The Human Protein Atlas databases were used to investigate the expression of Cathepsin A (CTSA) in hepatocellular carcinoma (HCC) and normal liver tissues to determine the relationship between prognosis of HCC and CTSA expression[24,25,26]
We found that the expression of CTSA mRNA in a variety of tumor tissues was significantly higher than normal tissues in the GEPIA database (Fig. 1A)
Summary
Hepatocellular carcinoma (HCC) has a high mortality rate and is one of the cancers in which incidence gradually increased in recent y ears[1,2]. Cathepsins were expressed in various types and stages of human cancer and were reported to be related to cancer progression and drug resistance[8,9,10]. Cathepsin K was found to have a high correlation with the progression of prostate cancer and breast cancer[17,18]. CTSA overexpression has been observed in various types of human cancers such as breast cancer, lung cancer, and prostate c ancer[20,21,22,23]. The gene expression profiling interactive analysis (GEPIA), The Cancer Genome Atlas (TCGA), The Human Protein Atlas databases were used to investigate the expression of CTSA in HCC and normal liver tissues to determine the relationship between prognosis of HCC and CTSA expression[24,25,26]. We performed gene set enrichment analysis (GSEA) analysis to determine the enriched genes and whether a series of previously-defined 9 stages of HCC progress-related gene sets were enriched in different p henotypes[28]
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