Identification of Specific Cell Subpopulations and Marker Genes in Ovarian Cancer Using Single-Cell RNA Sequencing.

Abstract

OBJECTIVE:

Ovarian cancer is the deadliest gynaecological cancer globally. In our study, we aimed to analyze specific cell subpopulations and marker genes among ovarian cancer cells by single-cell RNA sequencing (RNA-seq).

METHODS:

Single-cell RNA-seq data of 66 high-grade serous ovarian cancer cells were employed from the Gene Expression Omnibus (GEO). Using the Seurat package, we performed quality control to remove cells with low quality. After normalization, we detected highly variable genes across the single cells. Then, principal component analysis (PCA) and cell clustering were performed. The marker genes in different cell clusters were detected. A total of 568 ovarian cancer samples and 8 normal ovarian samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes were identified according to ∣log2fold change (FC) | >1 and adjusted p value <0.05. To explore potential biological processes and pathways, functional enrichment analyses were performed. Furthermore, survival analyses of differentially expressed marker genes were performed.

RESULTS:

After normalization, 6000 highly variable genes were identified across the single cells. The cells were divided into 3 cell populations, including G1, G2M, and S cell cycles. A total of 1,124 differentially expressed genes were identified in ovarian cancer samples. These differentially expressed genes were enriched in several pathways associated with cancer, such as metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway. Furthermore, marker genes, STAT1, ANP32E, GPRC5A, and EGFL6, were highly expressed in ovarian cancer, while PMP22, FBXO21, and CYB5R3 were lowly expressed in ovarian cancer. These marker genes were positively associated with prognosis of ovarian cancer.

CONCLUSION:

Our findings revealed specific cell subpopulations and marker genes in ovarian cancer using single-cell RNA-seq, which provided a novel insight into the heterogeneity of ovarian cancer.

• Authors: Yan Li, Juan Wang, Fang Wang, Chengzhen Gao, Yuanyuan Cao, Jianhua Wang
• Journal: BioMed research international (Biomed Res Int) Vol. 2021 Pg. 1005793 ( 2021) ISSN: 2314-6141 [Electronic] United States
• PMID: 34660776 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Yan Li et al.

Chemical References

• Biomarkers, Tumor
• Neoplasm Proteins

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Cell Cycle (genetics)
• Cell Differentiation (genetics)
• Databases, Genetic
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genes, Neoplasm
• Humans
• Neoplasm Proteins (genetics, metabolism)
• Ovarian Neoplasms (genetics, pathology)
• Principal Component Analysis
• Prognosis
• RNA-Seq
• Single-Cell Analysis
• Survival Analysis