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.

Screening of Exosome-Derived Proteins and Their Potential as Biomarkers in Diagnostic and Prognostic for Pancreatic Cancer

“…In IPMN samples, the most notable alterations observed in the proteomics profile compared to healthy controls were the over-expression of KLKB1, LBP, SERPINA1, and CFB, and the downregulation of C3, C5, APOD, and C1QA. The plasma kallikrein (KLKB1) is recurrently suggested as a biomarker for different types of carcinoma [ 29 ], but has also been previously detected on serum samples from IPMN patients [ 30 ], and benign pancreatic diseases [ 31 ], while alpha-1-antitrypsin (SERPINA1) over-expression was previously detected in plasma and suggested as a biomarker for pancreatic cancer, influencing inflammatory response, blood clotting, and immunity [ 32 , 33 ] Otherwise, the decreased expression of the human plasmatic apolipoprotein D (APOD) has been related to poor survival and worse prognosis in several cancer types [ 34 ].…”