Background: <p>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.</p> Methods: <p>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-<InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\beta\)</EquationSource> </InlineEquation> (TGF-<InlineEquation ID="IEq2"> <EquationSource Format="TEX">\(\beta\)</EquationSource> </InlineEquation>) pathway and drug response prediction were analyzed.</p> Results: <p>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-<InlineEquation ID="IEq3"> <EquationSource Format="TEX">\(\beta\)</EquationSource> </InlineEquation> receptors to regulate downstream genes. FUT11 could be applied in chemo-resistance prediction and drug discovery.</p> Conclusions: <p>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.</p>

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

  • Qi Chen,
  • Zhibin Liu,
  • Junpei Wang,
  • Yu Teng,
  • Mei Jiang,
  • Wentao Yue

摘要

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- \(\beta\) (TGF- \(\beta\) ) 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- \(\beta\) 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.