Unveiling Carbonic Anhydrase VIII, X, XI Expression in Cancer and Neurological Diseases Through Integrated Bioinformatics Approaches

Carbonic anhydrases are metalloenzymes found both in vertebrates and invertebrates. The CAs catalyze the reversible hydration of CO₂ to bicarbonate and H+ ions and play a significant role in respiration, transport of CO₂, pH homeostasis, electrolyte secretion, and biosynthetic reactions. The enzymatic activity of CAs is due to the coordination of Zn²⁺ in the active site by three histidine residues; however, in humans, there are three CAs known as CA-related proteins (CARPs) that are catalytically inactive due to the absence of one or more of the three histidine residues required for the coordination of the Zn²⁺ in the active site. Studies have shown that CARPs are expressed in all parts of the brain and are overexpressed in some cancers suggesting that the CARPs play a crucial role in neurological disorders and the development of cancer. However, the precise physiological roles of CARPs are still an enigma. In this study, we present a comprehensive biological workflow that employs various machine learning methodologies and statistical procedures to assess the similarity across CARPs by evaluating shared biological parameters. This approach enabled us to identify potential biomarkers, including transcription factors, co-expressed genes, and phenotypes, that may influence the expression of CARPs within disease pathways. Furthermore, we proposed a computational human health model by analyzing drugs and chemical candidates to prioritize compounds that may modulate regulatory networks associated with CARPs. These computational analyses identified candidate compounds for future experimental investigation in the context of neurological disorders and cancer.