Nonobstructive azoospermia (NOA) is one of the most severe types of male infertility. Amino acid metabolism (AAM) is strongly associated with various diseases. This study intended to identify biomarkers related to AAM in NOA. Biomarkers were screened from GSE9210, GSE108886, and AAM-related genes through a series of bioinformatics analyses. Then, the diagnostic efficacy of the biomarkers was evaluated. Furthermore, the mechanisms of action of these biomarkers were investigated through enrichment analysis, immune infiltration analysis, construction of regulatory networks, prediction of potential drugs, and prediction of related diseases. Finally, reverse transcription-quantitative polymerase chain reaction was performed for verification. Three biomarkers (AKT1, ASNS, and SHC1) were derived, which demonstrated good diagnostic efficacy for NOA. Meanwhile, AKT1, ASNS, and SHC1 might play significant roles in the development of male germ cells through pathways such as male gamete generation, sexual reproduction, and gamete generation. Immune infiltration analysis revealed these 3 biomarkers were closely associated with T follicular helper cells, resting natural killer cells, and regulatory T cells. And AKT1, ASNS, and SHC1 were regulated by 24 transcription factors and 15 microRNAs. Remarkably, sodium selenite, aflodac, and genistein were commonly predicted by the biomarkers. In addition, lung neoplasms were associated with AKT1, lipoidosis was associated with ASNS, and drug-induced acute liver injury was associated with SHC1. Ultimately, AKT1 and SHC1 were significantly upregulated in NOA. This study identified 3 biomarkers as being associated with NOA, providing valuable clues to help treat and predict NOA.
Guo et al. (Fri,) studied this question.