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已发表论文
CDCA3 调节肿瘤相关巨噬细胞极化以促进肝细胞癌的恶性进展
Authors Lyu S , Wang E, Lyu J, Xu H, Zhang D, Fang Z, Zhang L
Received 27 August 2025
Accepted for publication 19 December 2025
Published 28 December 2025 Volume 2025:12 Pages 3029—3047
DOI https://doi.org/10.2147/JHC.S559772
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 5
Editor who approved publication: Prof. Dr. Imam Waked
Shanmei Lyu,1,* Enqin Wang,2,* Juan Lyu,1 Hongkun Xu,1 Daochang Zhang,1 Zhijun Fang,1 Lihong Zhang1
1Clinical Laboratory of Shaoxing People’s Hospital, The First Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 2Department of Pathology, Wuchuan Country People’s Hospital, Zunyi, 564300, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lihong Zhang, Clinical Laboratory of Shaoxing People’s Hospital, The First Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China, Email whb0575@163.com
Background: Tumor-associated macrophages (TAMs) are pivotal components of the immune cell infiltrate in tumors and cell division cycle-associated protein-3 (CDCA3) is associated with tumor progression. The role of CDCA3 in regulating TAM polarization remains uncharacterized in hepatocellular carcinoma (HCC).
Methods: CDCA3 expression, its correlation with immune cell infiltration, and prognostic significance in HCC were analyzed using the TCGA and TIMER databases. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), were performed to predict CDCA3-related pathways. The knockdown efficiency of CDCA3 in HCC cell lines was confirmed by RT-qPCR and Western blotting. Functional assays, including CCK-8, wound healing, and flow cytometry, were used to assess the role of CDCA3 in cell proliferation, migration, and apoptosis. Immunohistochemistry (IHC) was applied to evaluate the correlation between CDCA3 expression and M2 macrophage markers in clinical tissue samples.
Results: Bioinformatic analysis revealed that CDCA3 was significantly upregulated in HCC tissues, and its high expression was associated with advanced clinical stage, higher tumor grade, and poor prognosis. CDCA3 expression also correlated strongly with the level of immune infiltration. Notably, CDCA3 showed high diagnostic potential for HCC, with an area under the curve (AUC) of 0.869, cut-off value of 189.03 pg/mL, sensitivity of 81.9%, and specificity of 77.8%. Experimentally, CDCA3 knockdown significantly suppressed malignant phenotypes of HCC cells and inhibited M2 macrophage polarization.
Conclusion: Our findings suggest that CDCA3 promotes the malignant progression of HCC by driving M2-like TAM polarization, potentially through the upregulation of cytokines such as TGF-β 1, VEGFA, CD40, CXCL1, and CXCL5. CDCA3 thus represents a promising diagnostic biomarker and therapeutic target for HCC.
Keywords: hepatocellular carcinoma, CDCA3, tumor-associated macrophages, malignant progression
1Clinical Laboratory of Shaoxing People’s Hospital, The First Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 2Department of Pathology, Wuchuan Country People’s Hospital, Zunyi, 564300, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lihong Zhang, Clinical Laboratory of Shaoxing People’s Hospital, The First Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China, Email whb0575@163.com
Background: Tumor-associated macrophages (TAMs) are pivotal components of the immune cell infiltrate in tumors and cell division cycle-associated protein-3 (CDCA3) is associated with tumor progression. The role of CDCA3 in regulating TAM polarization remains uncharacterized in hepatocellular carcinoma (HCC).
Methods: CDCA3 expression, its correlation with immune cell infiltration, and prognostic significance in HCC were analyzed using the TCGA and TIMER databases. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), were performed to predict CDCA3-related pathways. The knockdown efficiency of CDCA3 in HCC cell lines was confirmed by RT-qPCR and Western blotting. Functional assays, including CCK-8, wound healing, and flow cytometry, were used to assess the role of CDCA3 in cell proliferation, migration, and apoptosis. Immunohistochemistry (IHC) was applied to evaluate the correlation between CDCA3 expression and M2 macrophage markers in clinical tissue samples.
Results: Bioinformatic analysis revealed that CDCA3 was significantly upregulated in HCC tissues, and its high expression was associated with advanced clinical stage, higher tumor grade, and poor prognosis. CDCA3 expression also correlated strongly with the level of immune infiltration. Notably, CDCA3 showed high diagnostic potential for HCC, with an area under the curve (AUC) of 0.869, cut-off value of 189.03 pg/mL, sensitivity of 81.9%, and specificity of 77.8%. Experimentally, CDCA3 knockdown significantly suppressed malignant phenotypes of HCC cells and inhibited M2 macrophage polarization.
Conclusion: Our findings suggest that CDCA3 promotes the malignant progression of HCC by driving M2-like TAM polarization, potentially through the upregulation of cytokines such as TGF-β 1, VEGFA, CD40, CXCL1, and CXCL5. CDCA3 thus represents a promising diagnostic biomarker and therapeutic target for HCC.
Keywords: hepatocellular carcinoma, CDCA3, tumor-associated macrophages, malignant progression