AUTHOR=Zhang Bo , Wang Gang , Huang Cheng Bing , Zhu Jian Nan , Xue Yong , Hu Jian 

TITLE=Exploration of the Role of Serine Proteinase Inhibitor A3 in Alcohol Dependence Using Gene Expression Omnibus Database

JOURNAL=Frontiers in Psychiatry

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.779143

DOI=10.3389/fpsyt.2021.779143

ISSN=1664-0640

ABSTRACT=<p><bold>Background:</bold> Alcohol dependence is an overall health-related challenge; however, the specific mechanisms underlying alcohol dependence remain unclear. Serine proteinase inhibitor A3 (<italic>SERPINA3</italic>) plays crucial roles in multiple human diseases; however, its role in alcohol dependence clinical practice has not been confirmed.</p><p><bold>Methods:</bold> We screened Gene Expression Omnibus (GEO) expression profiles, and identified differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were generated using STRING and Cytoscape, and the key clustering module was identified using the MCODE plugin. <italic>SERPINA3</italic>-based target microRNA prediction was performed using online databases. Functional enrichment analysis was performed. Fifty-eight patients with alcohol dependence and 20 healthy controls were recruited. Clinical variables were collected and follow-up was conducted for 8 months for relapse.</p><p><bold>Results:</bold><italic>SERPINA3</italic> was identified as a DEG. <italic>ELANE</italic> and miR-137 were identified after PPI analysis. The enriched functions and pathways included acute inflammatory response, response to stress, immune response, and terpenoid backbone biosynthesis. <italic>SERPINA3</italic> concentrations were significantly elevated in the alcohol dependence group than in healthy controls (<italic>P</italic> &lt; 0.001). According to the median value of <italic>SERPINA3</italic> expression level in alcohol dependence group, patients were divided into high <italic>SERPINA3</italic> (≥2677.33 pg/ml, <italic>n</italic> = 29) and low <italic>SERPINA3</italic> groups (&lt;2677.33 pg/ml, <italic>n</italic> = 29). Binary logistic analysis indicated that IL-6 was statistically significant (<italic>P</italic> = 0.015) Kaplan-Meier survival analysis did not indicate any difference in event-free survival between patients with low and high <italic>SERPINA3</italic> levels (<italic>P</italic> = 0.489) after 8 months of follow-up. Receiver characteristic curve analysis revealed that <italic>SERPINA3</italic> had an area under the curve of 0.921 (<italic>P</italic> &lt; 0.0001), with a sensitivity and specificity of 93.1 and 80.0%, respectively. Cox regression analysis revealed that aspartate transaminase level was a negative predictor of relapse (β = 0.003; hazard ratio = 1.003; <italic>P</italic> = 0.03).</p><p><bold>Conclusions:</bold><italic>SERPINA3</italic> level was remarkably elevated in patients with alcohol dependence than healthy controls, indicating that <italic>SERPINA3</italic> is correlated with alcohol dependence. However, <italic>SERPINA3</italic> may not be a potential predictive marker of relapse with patients in alcohol dependence.</p>