SPINK1 is a Potential Diagnostic and Prognostic Biomarker for Sepsis

Dexiu Chen,1 Zhangjing Shi,1 Xiaolan Gao,1 Yuxiang Yang,1 Xianying Lei,1,&ast; Yingchun Hu2,&ast; 1Department of Critical Care Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Emergency Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingchun Hu, Department of Emergency Medicine, The Affiliated Hospital, Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86-830-3165851, Email huyingchun913@swmu.edu.cn Xianying Lei, Department of Critical Care Medicine, The Affiliated Hospital, Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86-830-3165527, Email leixianying310@swmu.edu.cnPurpose: There are no satisfactory diagnostic biomarkers for sepsis. Accordingly, this study screened biomarkers valuable for sepsis diagnosis and prognosis using data-independent acquisition (DIA) combined with clinical data analysis.Patients and Methods: Serine protease inhibitor Kazal-type 1 (SPINK1) is a differentially expressed protein that was screened using DIA and bioinformatics in sepsis patients (n = 22) and healthy controls (n = 10). The plasma SPINK1 levels were detected using an enzyme-linked immunosorbent assay (ELISA) in an expanded population (sepsis patients, n = 52; healthy controls, n = 10). The diagnostic value of SPINK1 in sepsis was evaluated using receiver operating characteristic (ROC) curve analysis based on clinical data. The prognostic value of SPINK1 for sepsis was evaluated using correlation and survival analyses.Results: DIA quality control identified 78 differential proteins (72 upregulated and six downregulated), among which SPINK1 was highly expressed in sepsis. The ELISA results suggested that SPINK1 expression was significantly elevated in the sepsis group (P < 0.05). ROC analysis of SPINK1 yielded an area under the curve (AUC) of 0.9096. Combining SPINK1 with procalcitonin (PCT) for ROC analysis yielded an AUC of 1. SPINK1 expression was positively correlated with the Sequential Organ Failure Assessment (SOFA) score (r = 3497, P = 0.0053) and APACHE II score (r = 3223, P = 0.0106). High plasma SPINK1 protein expression was negatively correlated with the 28-day survival rate of patients with sepsis (P = 0.0149).Conclusion: The plasma of sepsis patients contained increased SPINK1 protein expression. Combining SPINK1 with PCT might have a high diagnostic value for sepsis. SPINK1 was associated with the SOFA score, APACHE II score, and the 28-day survival rate in patients with sepsis.Keywords: serine protease inhibitor Kazal-type 1, sepsis, DIA, PCT, biomarker