Integrative Transcriptomic Analysis Identifies CXCL12 as a Candidate Hub Gene Associated with CD4⁺ T-Cell Immune Network Remodeling in Secondary Lymphedema

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Secondary lymphedema is accompanied by a persistent chronic inflammatory response and remodeling of the immune microenvironment. Among them, CD4⁺ T cells and their functional subgroups play a crucial role. This study identified potential candidate molecules in the CD4⁺ T cell-related immune microenvironment, providing new research clues for subsequent mechanism-oriented intervention studies. Methods In this study, we used the hdWGCNA method to establish a co-expression network of CD4⁺ T cells in secondary lymphedema, enabling the identification of key immune regulatory modules. We performed differential expression analysis using bulk transcriptomics and systematically analyzed the immune microenvironment of secondary lymphedema using CIBERSORT, Hallmark ssGSEA, and CellChat. This study primarily relies on computational analysis, employing numerous bioinformatics tools and algorithms for data integration and interpretation, aiming to explore the potential regulatory role of CD4⁺ T cells in the immune microenvironment from a holistic perspective. To further verify the results of the computational analysis, the selected key genes were experimentally validated using qPCR in a mouse model. Furthermore, computational virtual cell knockout analysis was applied for the first time in single-cell analysis of secondary lymphedema to assess the potential regulatory roles of ke

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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