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Войти в исследования Current medicinal chemistry · 2026
Computational Analysis of Endothelial Cell-related Genes in Ovarian Cancer and Preliminary in vitro Validation of COL1A1.
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Li Zongtao, Xia Jianmei, Wang Haixia, Li Zhao, Xiong Jian, Zhao Na, Huang Rui
Аннотация
INTRODUCTION: Endothelial cells play a crucial role in tumor invasion and metastasis. This study explored endothelial cell-targeted therapies for ovarian cancer (OC).
METHODS: The scRNA-seq data were obtained from the Gene Expression Omnibus (GEO) database for cell clustering analysis. Key genes were identified through integrated analysis of bulk RNA-seq data from the GTEx and TCGA databases. Receptor-ligand interactions were inferred using the "CellChat" R package. Hub genes in endothelial cells were screened by hdWGCNA and intersected with protein-protein interaction (PPI) network analysis (cytoHubba) to obtain candidate genes. Biomarker genes were further selected using SVM-RFE and LASSO regression analysis. Drug prediction and immune infiltration analyses were subsequently performed. The role of COL1A1 was further investigated through in vitro cellular assays.
RESULTS: Eight major cell subpopulations, including T cells and endothelial cells, were identified, with intercellular communication mediated by ligand-receptor pairs such as HLA-C-KIR2DL3 and CD99-CD99 pairs. hdWGCNA classified 5 modules and obtained 50 hub genes, from which cytoHubba screened 10 key intersecting genes. LASSO regression and SVM-RFE jointly identified 5 signature genes (CAV1, COL1A1, COL3A1, PDGFRB, and TIMP3). The expression of these genes was correlated positively with StromalScore, ImmuneScore, and ESTIMATEScore. Predicting cytarabine, genistein, and sorafenib were predicted as potential drugs for OC. COL1A1 knockdown inhibited the viability, migration, and invasion of OC cells in vitro.
DISCUSSION: This study identified endothelial cells as an OC subpopulation and discovered 5 potential biomarker genes related to angiogenesis, immune infiltration, and prognosis in OC. Potential drugs for the treatment of OC were predicted, but further validations are also required.
CONCLUSION: Our research revealed new clusters of endothelial cells in OC and identified potential biomarkers, contributing to the OC treatment that targets endothelial cells.
METHODS: The scRNA-seq data were obtained from the Gene Expression Omnibus (GEO) database for cell clustering analysis. Key genes were identified through integrated analysis of bulk RNA-seq data from the GTEx and TCGA databases. Receptor-ligand interactions were inferred using the "CellChat" R package. Hub genes in endothelial cells were screened by hdWGCNA and intersected with protein-protein interaction (PPI) network analysis (cytoHubba) to obtain candidate genes. Biomarker genes were further selected using SVM-RFE and LASSO regression analysis. Drug prediction and immune infiltration analyses were subsequently performed. The role of COL1A1 was further investigated through in vitro cellular assays.
RESULTS: Eight major cell subpopulations, including T cells and endothelial cells, were identified, with intercellular communication mediated by ligand-receptor pairs such as HLA-C-KIR2DL3 and CD99-CD99 pairs. hdWGCNA classified 5 modules and obtained 50 hub genes, from which cytoHubba screened 10 key intersecting genes. LASSO regression and SVM-RFE jointly identified 5 signature genes (CAV1, COL1A1, COL3A1, PDGFRB, and TIMP3). The expression of these genes was correlated positively with StromalScore, ImmuneScore, and ESTIMATEScore. Predicting cytarabine, genistein, and sorafenib were predicted as potential drugs for OC. COL1A1 knockdown inhibited the viability, migration, and invasion of OC cells in vitro.
DISCUSSION: This study identified endothelial cells as an OC subpopulation and discovered 5 potential biomarker genes related to angiogenesis, immune infiltration, and prognosis in OC. Potential drugs for the treatment of OC were predicted, but further validations are also required.
CONCLUSION: Our research revealed new clusters of endothelial cells in OC and identified potential biomarkers, contributing to the OC treatment that targets endothelial cells.