Abstract
BACKGROUND: Gliomas are the most prevalent primary tumors of the central nervous system. Their aggressive nature and the obstacles arising during therapy highlights the importance of finding new prognostic markers and therapy targets for gliomas. TXNDC genes are members of the thioredoxin superfamily and were shown to play a role in redox homeostasis, protein folding, electron transfer and also acting as cellular adapters. The well known contribution of these processes in cancer progression prompted us to investigate if TXNDC family members may also play a role in carcinogenesis, in particular diffuse gliomas. METHODS: The present study used in silico analysis tools GEPIA, UCSC Xena, Gliovis, cBioPortal, and Ivy GAP to evaluate the expression pattern, prognostic value and clinical significance of TXNDC family members in diffuse gliomas. RESULTS: Our analysis showed that TXNDC family members' expression pattern differ between tumors and healthy tissues and among tumors with different grades. The detailed analysis of TXNDC5 in glioma pathogenesis revealed that TXNDC5 expression is associated with more aggressive clinical and molecular features and poor therapy success both in LGG and GBM samples. Kaplan-Meier survival curves represented a worse prognosis for patients with leveated TXNDC5 levels in LGG and all grade glioma patients. The levels of TXNDC5 was shown to be possibly regulated by hypoxia-ER stress axis and a potential mechanism for TXNDC5-driven glioma progression was found to be extracellular matrix (ECM) production which is known to promote tumor aggressiveness. CONCLUSIONS: Our results uncovered the previously unknown role of TXNDC family members in glioma pathogenesis and showed that TXNDC5 levels could serve as a predictor of clinical outcome and therapy success and may very well be used for targeted therapy.