Alpha-1-antichymotrypsin as a novel biomarker for diagnosis, prognosis, and therapy prediction in human diseases

The glycoprotein alpha-1-antichymotrypsin (AACT), a serine protease inhibitor, is mainly synthesized in the liver and then secreted into the blood and is involved in the acute phase response, inflammation, and proteolysis. The dysregulation of AACT and its glycosylation levels are associated with tumor progression and recurrence, and could be used as a biomarker for tumor monitoring. In this review, we summarized the expression level, glycosylation modification, and biological characteristics of AACT during inflammation, neurodegenerative or other elderly diseases, and tumorigenesis, as well as, focused on the biological roles of AACT in cancer. The aberrant expression of AACT in cancer might be due to genetic alterations and/or immune by bioinformatics analysis. Moreover, AACT may serve as a diagnostic or prognostic biomarker or therapeutic target in tumors. Furthermore, we found that the expression of AACT was associated with the overall survival of patients with human cancers. Decreased AACT expression was associated with poor survival in patients with liver cancer, increased AACT expression was associated with shorter survival in patients with pancreatic cancer, and decreased AACT expression was associated with shorter survival in patients with early lung cancer. The review confirmed the key roles of AACT in tumorigenesis, suggesting that the glycoprotein AACT may serve as a biomarker for tumor diagnosis and prognosis, and could be a potential therapeutic target for human diseases.