卵巢癌
癌症研究
生物
卵巢癌
间质细胞
肿瘤微环境
癌症
浆液性液体
癌细胞
内科学
医学
遗传学
生物化学
肿瘤细胞
作者
Robson Francisco Carvalho,Luísa Matos do Canto,Cecilie Abildgaard,Mads Malik Aagaard,Monica Søgaard Tronhjem,Marianne Waldstrøm,Lars Henrik Jensen,Karina Dahl Steffensen,Sílvia Regina Rogatto
标识
DOI:10.1186/s12964-022-00991-4
摘要
Serous ovarian carcinoma is the most frequent histological subgroup of ovarian cancer and the leading cause of death among gynecologic tumors. The tumor microenvironment and cancer-associated fibroblasts (CAFs) have a critical role in the origin and progression of cancer. We comprehensively characterized the crosstalk between CAFs and ovarian cancer cells from malignant fluids to identify specific ligands and receptors mediating intercellular communications and disrupted pathways related to prognosis and therapy response.Malignant fluids of serous ovarian cancer, including tumor-derived organoids, CAFs-enriched (eCAFs), and malignant effusion cells (no cultured) paired with normal ovarian tissues, were explored by RNA-sequencing. These data were integrated with single-cell RNA-sequencing data of ascites from ovarian cancer patients. The most relevant ligand and receptor interactions were used to identify differentially expressed genes with prognostic values in ovarian cancer.CAF ligands and epithelial cancer cell receptors were enriched for PI3K-AKT, focal adhesion, and epithelial-mesenchymal transition signaling pathways. Collagens, MIF, MDK, APP, and laminin were detected as the most significant signaling, and the top ligand-receptor interactions THBS2/THBS3 (CAFs)-CD47 (cancer cells), MDK (CAFs)-NCL/SDC2/SDC4 (cancer cells) as potential therapeutic targets. Interestingly, 34 genes encoding receptors and ligands of the PI3K pathway were associated with the outcome, response to treatment, and overall survival in ovarian cancer. Up-regulated genes from this list consistently predicted a worse overall survival (hazard ratio > 1.0 and log-rank P < 0.05) in two independent validation cohorts.This study describes critical signaling pathways, ligands, and receptors involved in the communication between CAFs and cancer cells that have prognostic and therapeutic significance in ovarian cancer. Video abstract.
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