Favorable Prognostic Impact of Cathepsin H (CTSH) High Expression in Thyroid Carcinoma.

Background: Presently, no study reported the function of cathepsin H (CTSH) in thyroid carcinoma (THCA). The aim of present study was to initially explore the factors affecting CTSH expression, and association between CTSH expression and survival rate in THCA.

Methods: We explored mRNA expression of CTSH in normal and BRCA tissues, and evaluated prognostic impact of CTSH expression on the overall survival of THCA patients. Then, related factors influencing CTSH mRNA expression in THCA were analyzed. Functional enrichment analysis was performed to reveal the potential function of CTSH involved in THCA. We also constructed PPI network among co-expressed genes of CTSH to determine hub genes, followed by association analysis on hub genes with CTSH.

Results: (1) CTSH mRNA was highly expressed in THCA compared with normal group (<0.001). High expression of CTSH was conducive to the overall survival of THCA patients (=0.0027). CTSH was then determined as an independent prognostic factor in THCA (=0.024). (2) The mRNA expression of CTSH was statistically related to patient's histological type, N stage, T stage, tumor stage and sample type (all <0.001). CTSH copy number variation and methylation also influenced its mRNA expression (all <0.001). (3) Pathway analysis indicated that CTSH mainly participated in cancer-related pathways, such as hedgehog signaling pathway, cytokine-cytokine receptor interaction and JAK-STAT signaling pathway (all <0.05). (4) The top 10 co-expressed genes in whole PPI network showed significant correlation with CTSH expression (all <0.001).

Conclusion: CTSH higher expression was observed in THCA, which caused a good prognosis of patients. CTSH expression might be regulated by multiple factors including clinical characteristic, methylation, copy number and other genes. This study demonstrated the clinical significance of CTSH in THCA, as well as revealed the potential pathway associated with CTSH involved in thyroid cancer.