Assessment of Annexin A3 as a Potential Biomarker for Sepsis in Critically Ill Patients: A Meta-analysis and Retrospective Cohort Study

Background Current research indicated the comprehensive investigation of Annexin A3 (ANXA3) in sepsis patients remain uncertain. The aim of this research is to investigate the potential of ANXA3 as a biomarker for prediction of sepsis. Methods We performed a meta-analysis utilizing public datasets from Gene Expression Omnibus (GEO) and Array Express database to summarize and evaluate the expression of ANXA3 in sepsis patients. Then, we conducted a retrospective study to explore the role of plasma ANXA3 in 153 critically ill patients. Furthermore, the predictive ability of ANXA3, procalcitonin (PCT), interleukin-6 (IL-6) and Sequential Organ Failure Assessment (SOFA) score for the occurrence of sepsis were evaluated using the Area Under the Curve (AUC). Results Totally, the meta-analysis including 3241 sepsis and 1088 controls indicated sepsis patients were with markedly higher levels of ANXA3 mRNA expression (SMD = 2.01(1.54-2.48); P < 0.001). Meanwhile, sepsis deaths (n = 552) were with limited higher expression of ANXA3 mRNA than sepsis survivors (n = 2004) (SMD = 0.14(0.04-0.24); P < 0.01). Furthermore, our results indicated increased plasma ANXA3 on admission were significantly associated with the incidence of sepsis in critically ill patients (OR = 2.41(1.75-3.32), P < 0.001). As a predictive biomarker, plasma ANXA3 resulted in a better AUC 0.815(0.745-0.886) than PCT (0.673(0.584-0.761)) and IL-6 (0.672(0.585-0.759)) and SOFA score (0.668(0.577-0.759)). Additionally, patients with higher plasma ANXA3 had a poorer overall 28-day survival in critically ill patients (HR = 2.16(1.09-4.28); P < 0.05), but not for sepsis patients (HR = 1.63(0.65-4.06); P > 0.05). Conclusions Our study indicated increased ANXA3 obtained a good predictive ability for sepsis. Meanwhile, plasma ANXA3 was associated with mortality of critically ill patients, but not sepsis patients. The use of ANXA3 as a biomarker in sepsis patients require further evaluation in larger studies.