Pan-cancer analysis reveals potential for synergy between SERPINA1 molecular targeting and macrophage-related immunotherapy

Abstract Background The immune response can be modulated by autophagy to alter tumor growth. SERPINA1 is not only an autophagy-related protein but also a serine protease inhibitor with the potential for immunotherapy and targeted drug therapy. Methods Based on the latest multi-omic databases, we evaluated SERPINA1 mRNA and protein expression levels, prognostic value, methylation and mutation, signaling pathway, and gene ontology analysis and explored their relevance. The relationship between SERPINA1 expression and immune and drug sensitivity was also analyzed. Single-cell sequencing was used to validate the function and immunity in different cancers. Results Many tumors are associated with abnormal SERPINA1 expression and a poor prognosis. According to our study, DNA methylation, gene mutations, and post-translational modifications of SERPINA1 were significantly and positively correlated with its expression levels in breast cancer as a diagnostic marker. In addition, we observed that SERPINA1 positively correlates with macrophages and was able to stimulate M2 macrophage polarization, It was found that SERPINA1 was associated with macrophages in glioma immune microenvironments. Conclusions Considering that SERPINA1 plays a role in cancer progression, SERPINA1 may be a new promising target for immunotherapy and drug target therapy.