Downregulation of JKAP is correlated with elevated disease risk, advanced disease severity, higher inflammation, and poor survival in sepsis

Abstract

Objective: This study aimed to explore the association of JKAP with sepsis risk and investigate its correlation with disease severity, inflammatory cytokines, and survival in sepsis patients.

Methods: A hundred and one sepsis patients along with 100 healthy controls were enrolled, and their blood serum samples were collected for JKAP and inflammatory cytokines measurement by enzyme-linked immunoassay. The difference in serum JKAP between sepsis patients and healthy controls was determined. Among sepsis patients, the correlation of JKAP with disease severity, laboratory indexes, inflammatory cytokines, 28-day mortality, and accumulating survival was analyzed.

Results: JNK pathway-associated phosphatase level was decreased in sepsis patients compared with healthy controls and presented with good value in predicting decreased sepsis risk (AUC = 0.896 [95% CI: 0.851-0.941]). And its low expression was associated with advanced disease severity (APACHE II score and SOFA score) and systemic inflammation (CRP, PCT, TNF-α, IL-1β, IL-6, and IL-17) in sepsis patients. Additionally, JKAP level was decreased in deaths compared with survivors and had good value in distinguishing deaths from survivors (AUC = 0.742 [95% CI: 0.636-0.849]). Further, Kaplan-Meier curve analysis disclosed that JKAP high expression predicted more prolonged accumulating survival in sepsis patients.

Conclusion: JNK pathway-associated phosphatase is of good value in predicting lower sepsis risk, and its downregulation correlates with advanced disease severity, higher level of systemic inflammation, and poor survival in sepsis patients.

Keywords: JNK pathway-associated phosphatase; disease risk; inflammation; sepsis; survival.

Figure 1

The predictive value of JKAP level in sepsis risk. The JKAP was decreased in sepsis patients compared with healthy controls (A). The comparison of JKAP level between sepsis patients and healthy controls was determined by Wilcoxon rank‐sum test. And JKAP was of great value in distinguishing sepsis patients from healthy controls (B). ROC curve was performed to evaluate the ability of JKAP level to discriminate sepsis patients from healthy controls. P < 0.05 was considered significant. JKAP, JNK pathway–associated phosphatase; ROC, receiver operating characteristic

Figure 2

The prognostic value of JKAP level in sepsis. Death and survival accounted for 32.7% and 67.3% of total sepsis patients (A). Among all the sepsis patients, the JKAP level was decreased in death compared with survival (B). The comparison of JKAP level between death and survival was conducted by Wilcoxon rank‐sum test. JKAP was of value in determining death from survival in sepsis patients (C). ROC curve was conducted to assess the ability of JKAP to differentiate death from survival. P < 0.05 was considered significant. JKAP, JNK pathway–associated phosphatase; ROC, receiver operating characteristic

Figure 3

The accumulating survival of total sepsis patients, JKAP high group, and JKAP low group. The mean value of accumulating survival for total sepsis patients was exhibited by Kaplan‐Meier curve (A). And the mean value of accumulating survival was increased in JKAP high group compared with JKAP low group (B). The comparison of survival between JKAP high group and JKAP low group was conducted by log‐rank test. P < 0.05 was considered significant. JKAP, JNK pathway–associated phosphatase