Chronic inflammation and immune dysregulation are associated with atherosclerosis in gynecologic malignancies: roles of endothelial activation and cytokine networks
Year: 2026
Type: article
Study design: Observational Study
Abstract: Cancer-related inflammation and immune dysregulation may promote endothelial activation and accelerate subclinical atherosclerosis in gynecologic malignancies. In this observational cohort, 600 patients with gynecologic cancer and 200 controls underwent baseline biomarker profiling and carotid ultrasonography. In the present study, carotid atherosclerosis was operationalized as ultrasound-detected carotid plaque presence (binary yes/no), while cIMT and plaque area were evaluated as secondary continuous vascular phenotypes. Biomarkers spanned systemic inflammation/cytokines, immune phenotypes (Treg, NK, MDSC), and endothelial activation (VCAM-1). Multivariable logistic regression (stepwise and mutually adjusted models), unsupervised clustering, mediation analysis, and LASSO-based prediction modeling were performed; MACE was evaluated during follow-up in the cancer cohort. Atherosclerosis prevalence was higher in the cancer cohort than controls (22.3% [134/600] vs. 10.0% [20/200]). In mutually adjusted analyses, VCAM-1 remained the strongest independent correlate of atherosclerosis (OR = 2.91, 95% CI 1.95–4.34), whereas NK cells were inversely associated (OR = 0.64, 95% CI 0.46–0.89). Clustering identified a “high inflammation–high immunosuppression–high endothelial activation” phenotype with markedly higher atherosclerosis prevalence (38.5% vs. 8.6%; unadjusted OR = 6.65). VCAM-1 partially mediated the immune dysregulation–atherosclerosis association (OR indirect = 1.19; proportion mediated 14.8%). The combined (clinical + biomarkers) model improved discrimination (AUC 0.880 vs. 0.786). Over a median 36.95 months, 69 MACE events occurred; baseline binary ultrasound-defined carotid atherosclerosis independently predicted MACE (HR = 1.75, 95% CI 1.01–3.02), while the high-dysregulation phenotype was borderline after full adjustment (HR = 1.63, P = 0.070). In gynecologic malignancies, endothelial activation, captured by VCAM-1, appears central to linking immune dysregulation with ultrasound-defined carotid atherosclerosis, and baseline binary ultrasound-defined carotid atherosclerosis was associated with subsequent MACE. Proposed cardio-oncology pathway linking gynecologic cancer to atherosclerotic cardiovascular risk. Gynecologic cancer is associated with heightened systemic inflammation (hsCRP, IL-6) and immune dysregulation (↑Treg, ↑MDSC, ↓NK), which promote endothelial activation (↑VCAM-1, ↑ICAM-1, ↑E-selectin). Endothelial activation accelerates subclinical atherosclerosis (increased cIMT and plaque burden), translating into a higher risk of major adverse cardiovascular events (MACE). Each arrow represents an empirically testable association aligned with the study’s statistical models.
Source: BMC Cancer
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,390
OpenAlex ID: W7155503283