The diagnostic value of endoplasmic reticulum stress-related specific proteins GRP78 and CHOP in patients with sepsis: a diagnostic cohort study
Fangfang Li, Qionghua Lin, Lihua Shen, Zhongwei Zhang, Pengmei Wang, Shan Zhang, Qian Xing, Zhili Xia, Zhiyong Zhao, Yunhe Zhang, Biao Zhu
Abstract
Background: Sepsis is a life-threatening disease with high mortality. Early diagnosis is critical as early treatment improves outcomes. The protein levels of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), markers of endoplasmic reticulum stress (ERS) activation, were reported increasing rapidly and continuously in the serum of patients with sepsis. Therefore, they might serve as a potential biomarker for sepsis diagnosis. This study aimed to analyze the role of GRP78 and CHOP in the diagnosis of patients with sepsis. Methods: This study enrolled a total of 92 infected patients with or without sepsis who were admitted to the intensive care unit (ICU) from February 1, 2018 to September 30, 2018. According to 2016 SCCM/ESICM Sepsis 3.0 diagnostic criteria, patients with sepsis were allocated into group I (sepsis infected group) and patients without sepsis were allocated into group II (non-sepsis infected group). Serum samples were collected on days 1, 2, 3, and 7 after admission to ICU, and the concentrations of GRP78 and CHOP in the serum were analyzed by enzyme-linked immunosorbent assay (ELISA). The diagnostic ability of GRP78, CHOP, and other traditional inflammatory markers was assessed with receiver operating characteristic (ROC)/area under the ROC curves (AUC) analysis. Patients were shortly follow-up for the 28-day mortality. Results: Serum GRP78 and CHOP levels in group I patients were higher than that in group II patients (P=0.021, P=0.00, respectively). When GRP78 was used to diagnose sepsis, the maximum area under the ROC curve (AUC) was 0.771 (95% CI: 0.662-0.880) and the optimal threshold was 157.29 ng/L (sensitivity, 75.0%; specificity, 73.1%) on day 2. When CHOP was used for the diagnosis of sepsis, the maximum AUC was 0.813(95% CI: 0.721-0.906) and the optimal threshold was 4.915 ng/L (sensitivity, 57.7%; specificity, 96.2%) on day 2. Conclusions: Compared with traditional inflammatory markers, ERS-related specific proteins GRP78 and CHOP have better sensitivity and specificity in the diagnosis of sepsis, which is helpful for clinicians in the diagnosis of sepsis.