Single-cell transcriptomics uncovers heterogenous cell clusters and the biomarker FUT11 in ovarian cancer progression

BACKGROUND: Ovarian cancer (OC) is the most lethal of gynecological cancers and presents a poor prognosis due to difficulty in early diagnosis, extensive abdominal metastasis and chemo-resistance. We utilized single-cell transcriptomics to deconvolute intratumoral heterogeneity and identify biomarkers and therapeutic targets. METHODS: Single-cell RNA sequencing (scRNA-seq) were performed with 15 patient samples. Metastatic and chemo-resistant epithelial subclusters were discovered by copy-number variations (CNV), Kaplan–Meier and enrichment analysis. Fucosyltransferase 11 (FUT11) was identified by differential expression analysis and validated by in vitro assays. Cell-cell communication analysis and protein–protein interaction (PPI) network were conducted to discover pathways and receptors in FUT11 positive (FUT11+) cells. Function of FUT11 in transforming growth factor-β (TGF-β) pathway and drug response prediction were analyzed. RESULTS: Epithelial subcluster EC5 was associated with metastasis, chemo-resistance and poor prognosis of OC. FUT11 was a hub gene of EC5 and communicated with mesenchymal cells through TGF-β receptors to regulate downstream genes. FUT11 could be applied in chemo-resistance prediction and drug discovery. CONCLUSIONS: The present research provided new insights into gene signatures for tumor progression and drug discovery, and identified FUT11 as a diagnostic biomarker and therapeutic target.