Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

Background: T-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment. Methods: We examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database. Results: In gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all p<0.05). By combining the three potential biomarkers, a TTCC signature was developed, which retained a significant association with OS both in stage IV and stage I-III patients. In lung and ovarian cancer, association with OS was also significant when all tumour stages were considered, but was partly lost or inconclusive after splitting cases into localized and metastatic subsets. Conclusions: Alterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation.