Thrombomodulin and CXCL6 Altered Expression in Preeclampsia: Serum‐Placental Biomarker Correlations and Clinical Significance

Objective We aimed to examine the expression levels of thrombomodulin (THBD) and C‐X‐C motif ligand 6 (CXCL6/GCP‐2) in the serum and placental tissues of pregnant women with preeclampsia (PE) and assess their clinical significance. Methods In this cross‐sectional study, a cohort comprising 96 pregnant women diagnosed with preeclampsia (PE) and 119 healthy pregnant counterparts was selected from Jiangxi Maternal and Child Health Hospital, encompassing January 2024 to December 2024. The levels of THBD and CXCL6 in serum and placental tissues were assessed. The Mann‒Whitney U test was used to compare the differences between two groups, and the Spearman test was used to evaluate the risk factors for PE via correlation analysis. Results Serum THBD and CXCL6 levels were significantly elevated in the PE group compared to controls ( p < 0.001), with a positive correlation between the two markers ( r = 0.41, p < 0.001). Immunohistochemical analysis demonstrated reduced THBD and CXCL6 expression in placental syncytiotrophoblasts ( p < 0.05), alongside diminished THBD immunoreactivity in vascular endothelial cells ( p < 0.05). Multivariate logistic regression identified CXCL6, uric acid (UA), and lactate dehydrogenase (LDH) as independent risk factors for PE, while albumin (Alb) emerged as a protective factor ( p < 0.05). Conclusions In pregnant women with PE, the serum levels of THBD and CXCL6 are increased, whereas their expression in placental tissue is decreased. CXCL6 emerges as an independent risk factor for PE, with expression patterns independent of gestational age confounding, while THBD shows PE‐specific gestational age‐related effects that provide additional insights into disease pathophysiology. These findings indicate that the inflammatory response and insufficient trophoblast invasion may play important roles in the pathogenesis of PE, providing a new theoretical basis for the early diagnosis and targeted intervention of PE.