Pan-cancer molecular signatures connecting aspartate transaminase to cancer prognosis, metabolic and immune signatures.

Serum aspartate transaminase (sAST) level is used routinely in conjunction with other clinical assays to assess liver health and disease. Increasing evidence suggests that sAST is associated with all-cause mortality and has prognostic value in several cancers, including gastrointestinal and urothelial cancers. Here, we undertake a systems approach to unravel molecular connections between AST and cancer prognosis, metabolism, and immune signatures at the transcriptomic and proteomic levels. We find that GOT1 and GOT2 expression is reversed in tumors relative to normal tissues whereby tumors residing in tissues that normally have low expression tend to have high GOT1/GOT2 expression and vice versa. Expression of GOT1 and GOT2 is associated with overall survival in several tumors across distinct tissues. At the proteomic level, expression of AST is associated with distinct pan-cancer molecular subtypes with an enrichment of specific metabolic and immune signatures. The GOT1 interactome is enriched with the targets of cancer-associated miRNAs, specifically mir34a - a promising cancer therapeutic, while the GOT2 interactome is enriched with proteins that interact with cancer-associated transcription factors. Our findings suggest that perturbations in the levels of GOT1/GOT2 within specific tissues reflect pathophysiological changes beyond tissue damage and have implications for cancer metabolism, immune infiltration, prognosis, and treatment personalization.