A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance.

Lactate dehydrogenase A (LDHA), a critical enzyme involved in glycolysis, is broadly involved multiple biological functions in human cancers. It is reported that can impact tumor immune surveillance and induce the transformation of tumor-associated macrophages, highlighting its unnoticed function of in immune system. However, in human cancers, the role of in prognosis and immunotherapy hasn't been investigated. In this study, we analyzed the expression pattern and prognostic value of in pan-cancer and explored its association between tumor microenvironment (TME), immune infiltration subtype, stemness scores, tumor mutation burden (TMB), and immunotherapy resistance. We found that expression is tumor heterogeneous and that its high expression is associated with poor prognosis in multiple human cancers. In addition, expression was positively correlated with the presence of mononuclear/macrophage cells, and also promoted the infiltration of a range of immune cells. Genomic alteration of was common in different types of cancer, while with prognostic value in pan-cancers. Pan-cancer analysis revealed that the significant correlations existed between expression and tumor microenvironment (including stromal cells and immune cells) as well as stemness scores (DNAss and RNAss) across cancer types. Drug sensitivity analysis also revealed that was able to predict response to chemotherapy and immunotherapy. Furthermore, it was confirmed that knockdown of reduced proliferation and migration ability of lung cancer cells. Taken together, could serve as a prognostic biomarker and a potential immunotherapy marker.