Integrating Single‐Cell and Spatial Transcriptomes in HGSOC to Decipher the Metastasis‐Associated Biomarkers

ABSTRACT High‐grade serous ovarian cancer (HGSOC) is the most common and lethal histological subtype of ovarian cancer. This study aimed to identify peritoneal metastasis‐associated biomarkers of HGSOC to provide directions for subsequent treatment. Transcriptome data were extracted from the GEO database and literature. Differential expression analysis, a PPI network, and machine learning were conducted to obtain key cells and biomarkers, followed by the construction of ROC curves and expression validation to screen biomarkers. The functional mechanism of the biomarkers was explored via a molecular regulatory network and enrichment analysis. Potential drugs targeting biomarkers were also predicted. Based on the single‐cell and spatial transcriptome data, the expression patterns and communication types of key cells and biomarkers were explored. CYTH1 and ARHGEF1 were identified as biomarkers, while ILCs, DC‐1, and macrophages were identified as key cells associated with metastasis in HGSOC. Spatial transcriptome data confirmed that the biomarkers are highly expressed in T and NK cells. Cell interaction analysis indicated that the expression of SPP1 was higher in peritoneal metastases than in primary lesions. Furthermore, in vitro studies demonstrated that macrophage‐derived SPP1 significantly enhanced the proliferation and migration of ovarian cancer cells. This study identifies CYTH1 and ARHGEF1 as metastatic biomarkers and implicates macrophages in promoting metastasis through SPP1, which provides new insights into the understanding of tumor metastatic mechanisms in HGSOC.