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Article Abstract

Background: () has been identified as a causative factor in the progression of colon cancer. This study aims to integrate bulk RNA-seq with single-cell RNA-seq (scRNA-seq) to elucidate the molecular mechanisms by which facilitates colon cancer progression.

Methods: The scRNA-seq data from tumor tissues of intervention were analyzed to screen cells with significant proportion changes. Differentially expressed genes of cells with different proportions were extracted and intersected with those identified in the bulk RNA-seq analysis. Three machine learning algorithms were employed to identify characteristic genes. Clinical tissue samples and external datasets, along with co-culture experiments, were utilized to validate these findings.

Results: Following intervention, there was an observed increase in the fibroblast iso-cellular ratio and interaction levels. Utilizing machine learning algorithms, we identified five key genes. The differential expression of Serpine2 was validated using clinical samples and external datasets. Furthermore, patients with metastatic colon cancer exhibited significantly higher Serpine2 expression compared to those without metastasis. was found to significantly enhance the expression of Serpine2 in fibroblasts and to promote the proliferation and migration capabilities of tumor cells.

Conclusion: This study elucidates the role of in promoting colon cancer progression through the enhancement of fibro-macrophage-epithelial cell interactions. Furthermore, Serpine2 has been identified as a potential molecular marker associated with -mediated colon cancer progression and metastasis. These findings contribute novel insights that may inform the development of therapeutic strategies for colon cancer.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240788PMC
http://dx.doi.org/10.3389/fimmu.2025.1563922DOI Listing

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