ChaC1 upregulation reflects poor prognosis in a variety of cancers: analysis of the major missense SNPs of ChaC1 as an aid to refining prognosis

The ChaC1 enzyme that catalyzes cytosolic glutathione degradation is highly upregulated in several cancers. In a systematic review of gene signature panels for cancer prognosis based on oxidative stress and ferroptosis genes, we observed that ChaC1 was found in panels in a wide variety of different cancers, with the upregulation correlating with poor prognosis. Since SNPs can have an impact on functionality and prognosis, ChaC1 SNPs from various databases were also investigated. Six frequently observed missense SNPs were chosen for reconstruction, and their functionality was evaluated. Three out of six SNPs resulted in either a partial or complete loss of ChaC1 function, and these SNPs had the changes R72Q, A156V, and G173S in their proteins. This study highlights the importance of ChaC1 in cancer prognosis across a wide variety of cancers. Additionally, the information on the SNPs of ChaC1 with altered enzymatic activities would improve the prognostic ability of these panels and facilitate treatment regimens.