Diagnostic value and mechanism of plasma S100A1 protein in acute ischemic stroke: a prospective and observational study
Authors: Hong Guo , Li Tingting , Zhao Haina , Zeng Zhaohao , Zhai Jinglei , Li Xiaobo , Luo Xiaoguang 
Published: January 2023

Background
Plasma S100A1 protein is a novel inflammatory biomarker associated with acute myocardial infarction and neurodegenerative disease’s pathophysiological mechanisms. This study aimed to determine the levels of this protein in patients with acute ischemic stroke early in the disease progression and to investigate its role in the pathogenesis of acute ischemic stroke.

Methods
A total of 192 participants from hospital stroke centers were collected for the study. Clinically pertinent data were recorded. The volume of the cerebral infarction was calculated according to the Pullicino formula. Multivariate logistic regression analysis was used to select independent influences. ROC curve was used to analyze the diagnostic value of AIS and TIA. The correlation between S100A1, NF-κB p65, and IL-6 levels and cerebral infarction volume was detected by Pearson correlation analysis.

Results
There were statistically significant differences in S100A1, NF-κB p65, and IL-6 among the AIS,TIA, and PE groups (S100A1, [230.96 ± 39.37] vs [185.85 ± 43.24] vs [181.47 ± 27.39], P < 0.001; NF-κB p65, [3.99 ± 0.65] vs [3.58 ± 0.74] vs [3.51 ± 0.99], P = 0.001; IL-6, [13.32 ± 1.57] vs [11.61 ± 1.67] vs [11.42 ± 2.34], P < 0.001). Multivariate logistic regression analysis showed that S100A1 might be an independent predictive factor for the diagnosis of disease (P < 0.001). The AUC of S100A1 for diagnosis of AIS was 0.818 (P < 0.001, 95% CI [0.749–0.887], cut off 181.03, Jmax 0.578, Se 95.0%, Sp 62.7%). The AUC of S100A1 for diagnosis of TIA was 0.720 (P = 0.001, 95% CI [0.592–0.848], cut off 150.14, Jmax 0.442, Se 50.0%, Sp 94.2%). There were statistically significant differences in S100A1, NF-κB p65, and IL-6 among the SCI,MCI, and LCI groups (S100A1, [223.98 ± 40.21] vs [225.42 ± 30.92] vs [254.25 ± 37.07], P = 0.001; NF-κB p65, [3.88 ± 0.66] vs [3.85 ± 0.64] vs [4.41 ± 0.45], P < 0.001; IL-6, [13.27 ± 1.65] vs [12.77 ± 1.31] vs [14.00 ± 1.40], P = 0.007). Plasma S100A1, NF-κB p65, and IL-6 were significantly different from cerebral infarction volume (S100A1, r = 0.259, P = 0.002; NF-κB p65, r = 0.316, P < 0.001; IL-6, r = 0.177, P = 0.036). There was a positive correlation between plasma S100A1 and IL-6 with statistical significance (R = 0.353, P < 0.001). There was no significant positive correlation between plasma S100A1 and NF-κB p65 (R < 0.3), but there was statistical significance (R = 0.290, P < 0.001). There was a positive correlation between IL-6 and NF-κB p65 with statistical significance (R = 0.313, P < 0.001).

Conclusion
S100A1 might have a better diagnostic efficacy for AIS and TIA. S100A1 was associated with infarct volume in AIS, and its level reflected the severity of acute cerebral infarction to a certain extent. There was a correlation between S100A1 and IL-6 and NF-κB p65, and it was reasonable to speculate that this protein might mediate the inflammatory response through the NF-κB pathway during the pathophysiology of AIS.