Background: Cysteine cathepsin C encoded by the CTSC gene is an important member of the cysteine cathepsin family that plays a key role regulation of many types of tumors. However, whether CTSC is involved in the pathological process of glioma has not yet been reported. We comprehensively analyzed data from multiple databases and for the first time revealed a role and specific mechanism of action of CTSC in glioma, identifying it as a novel and efficient biomarker for the diagnosis and treatment of this brain tumor.
Methods: The expression of CTSC in glioma and its relationship with clinical characteristics and prognosis of patients with glioma were analyzed at different levels by using clinical sample information from several databases. CTSC expression levels in glioma and normal brain tissues, as well as in glioma cells and normal brain cells, was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Gene set enrichment analysis (GSEA) was used to reveal the signaling pathways that CTSC may participate in. The connectivity map was used to reveal small molecules that may inhibit CTSC expression in glioma, and the putative effect of these compounds was verified by RT-qPCR.
Results: Our analyses showed that the expression of CTSC in glioma was higher than that in non-cancerous cells. GSEA showed that CTSC expression may regulate the malignant development of glioma through Toll-like receptor signaling pathways, pathways in cancer, and extracellular matrix receptor interaction signaling pathways. And we proved piperlongumine and scopoletin could inhibit CTSC expression in glioma cells.
Conclusions: CTSC may serve as an efficient molecular target for the diagnosis and therapy of glioma, thereby improving the poor prognosis of patients with glioma.
Keywords: Biomarker; Cysteine cathepsin C; Gene set enrichment; Glioma; Piperlongumine, scopoletin; Prognosis.
© 2021. The Author(s).