Liquan Gao, Zhiyao Chen, Yuhang Wang, Jie Gao, Ni Yan, KuanYe Huang
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引用次数: 0
Abstract
Background: Secondary lymphedema is a debilitating complication following oncologic surgery, characterized by progressive tissue fibrosis and chronic inflammation. Although transforming growth factor-beta 1 (TGF-β1) has been established as a central mediator of fibrotic remodeling, the broader interplay between pro-inflammatory cytokines and downstream fibrotic signaling cascades in post-surgical lymphedematous tissue remains poorly understood.
Methods: Skin and subcutaneous tissue biopsies were prospectively collected from 126 patients with unilateral breast cancer-related lymphedema and 58 matched controls across three tertiary centers between January 2024 and December 2025. Tissue specimens were analyzed using immunohistochemistry, quantitative real-time PCR, multiplex cytokine profiling, and Western blotting. Correlations between cytokine expression, fibrotic markers, and clinical severity were evaluated.
Results: Lymphedematous tissues exhibited significantly elevated expression of TGF-β1, interleukin-6 (IL-6), interleukin-13 (IL-13), and tumor necrosis factor-alpha (TNF-α) compared with controls (all P < 0.01). Concurrent activation of Smad2/3 and STAT3 signaling pathways was observed, with both correlating positively with disease severity. Multivariate regression identified TGF-β1, IL-6, and IL-13 as independent predictors of fibrotic burden, whereas TNF-α lost significance after adjustment for confounders. Lymphatic vessel density was inversely associated with cytokine levels and fibrotic severity.
Conclusion: Secondary upper extremity lymphedema following breast cancer surgery is driven by a coordinated inflammatory and fibrotic axis involving TGF-β1, IL-6, and IL-13 through convergent Smad2/3 and STAT3 signaling. These findings support the development of multi-pathway therapeutic strategies beyond single-agent anti-fibrotic approaches for post-surgical lymphedema.
期刊介绍：
Annals of Vascular Surgery, published eight times a year, invites original manuscripts reporting clinical and experimental work in vascular surgery for peer review. Articles may be submitted for the following sections of the journal:
Clinical Research (reports of clinical series, new drug or medical device trials)
Basic Science Research (new investigations, experimental work)
Case Reports (reports on a limited series of patients)
General Reviews (scholarly review of the existing literature on a relevant topic)
Developments in Endovascular and Endoscopic Surgery
Selected Techniques (technical maneuvers)
Historical Notes (interesting vignettes from the early days of vascular surgery)
Editorials/Correspondence
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