Exploring the cellular and molecular differences between ovarian clear cell carcinoma and high-grade serous carcinoma using single-cell RNA sequencing and GEO gene expression signatures.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37525249", "kind": "science-record", "revision": 4, "content_hash": "sha256:465a7e20bc21d27cb97d1c279d3f77e4950b9007c7f9ff115ead225368bd5f3e", "created_at": "2026-11-01T19:02:18Z", "updated_at": "2026-11-01T22:10:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring the cellular and molecular differences between ovarian clear cell carcinoma and high-grade serous carcinoma using single-cell RNA sequencing and GEO gene expression signatures.", "doi": "10.1186/s13578-023-01087-3", "pmid": "37525249", "authors": ["Dan Guo", "Sumei Zhang", "Yike Gao", "Jinghua Shi", "Xiaoxi Wang", "Zixin Zhang", "Yaran Zhang", "Yuming Wang", "Kun Zhao", "Mei Li", "Anqi Wang", "Pan Wang", "Yanqin Gou", "Miao Zhang", "Meiyu Liu", "Yuhan Zhang", "Rui Chen", "Jian Sun", "Shu Wang", "Xunyao Wu", "Zhiyong Liang", "Jie Chen", "Jinghe Lang"], "journal": "Cell & bioscience", "year": 2023, "abstract": "The two most prevalent subtypes of epithelial ovarian carcinoma (EOC) are ovarian clear cell carcinoma (OCCC) and high-grade serous ovarian carcinoma (HGSC). Patients with OCCC have a poor prognosis than those with HGSC due to chemoresistance, implying the need for novel treatment target. In this study, we applied single-cell RNA sequencing (scRNA-seq) together with bulk RNA-seq data from the GEO (Gene Expression Omnibus) database (the GSE189553 dataset) to characterize and compare tumor heterogeneity and cell-level evolution between OCCC and HGSC samples. To begin, we found that the smaller proportion of an epithelial OCCC cell subset in the G2/M phase might explain OCCC chemoresistance. Second, we identified a possible pathogenic OCCC epithelial cell subcluster that overexpresses LEFTY1. Third, novel biomarkers separating OCCC from HGSC were discovered and subsequently validated on a wide scale using immunohistochemistry. Amine oxidase copper containing 1 (AOC1) was preferentially expressed in OCCC over HGSC, while S100 calcium-binding protein A2 (S100A2) was detected less frequently in OCCC than in HGSC. In addition, we discovered that metabolic pathways were enriched in the epithelial compartment of the OCCC samples. In vitro experiments verified that inhibition of oxidative phosphorylation or glycolysis pathways exerted direct antitumor effects on both OCCC and HGSC cells, while targeting glutamine metabolism or ferroptosis greatly attenuated chemosensitivity only in OCCC cells. Finally, to determine whether there were any variations in immune cell subsets between OCCC and HGSC, data from scRNA-seq and mass cytometry were pooled for analysis. In summary, our work provides the first holistic insights into the cellular and molecular distinctions between OCCC and HGSC and is a valuable source for discovering new targets to leverage in clinical treatments to improve the poor prognosis of patients with OCCC.", "claims": [{"id": "claim-method", "statement": "To identify differentially expressed genes (DEGs), we used the FindMarkers function with two-sided unpaired Wilcoxon tests, and p values were adjusted following the Benjamin & Hochberg protocol.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37525249", "locator": "sections[14] \"Differentially expressed genes and pathway enrichment\" paragraph 2", "quote": "To identify differentially expressed genes (DEGs), we used the FindMarkers function with two-sided unpaired Wilcoxon tests, and p values were adjusted following the Benjamin & Hochberg protocol."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The accession number for the raw sequencing data has been deposited in the Genome Sequence Archive for humans (GSA-Human) under accession number HRA002536. To comply with the “Guidance of the Ministry of Science and Technology (MOST) for the Review and Approval of Human Genetic Resources”, we are required to deposit the genomic data of Chinese people under controlled access at the GSA in Beijing Institute of Genomics Data Center. To access the raw data under accession number HRA002536, please submit requests to the GSA-Human online page for this study (https://ngdc.cncb.ac.cn).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37525249", "locator": "sections[32] \"Data Availability\" paragraph 2", "quote": "The accession number for the raw sequencing data has been deposited in the Genome Sequence Archive for humans (GSA-Human) under accession number HRA002536. To comply with the “Guidance of the Ministry of Science and Technology (MOST) for the Review and Approval of Human Genetic Resources”, we are required to deposit the genomic data of Chinese people under controlled access at the GSA in Beijing Institute of Genomics Data Center. To access the raw data under accession number HRA002536, please submit requests to the GSA-Human online page for this study (https://ngdc.cncb.ac.cn)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study found distinct cellular and molecular differences between OCCC and HGSC, including biomarkers and metabolic pathways with potential therapeutic relevance.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37525249", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In summary, our work provides the first holistic insights into the cellular and molecular distinctions between OCCC and HGSC and is a valuable source for discovering new targets to leverage in clinical treatments to improve the poor prognosis of patients with OCCC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study found distinct cellular and molecular differences between OCCC and HGSC, including biomarkers and metabolic pathways with potential therapeutic relevance.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37525249"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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RNA-seq data processing Raw sequencing data generate"], "order_basis": "paper_text_order:91", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["subsequently validated on a wide scale using immunohistochemistry. Amine oxidase copper containing 1 (AOC1) wa", "formed to evaluate binary variables, such as immunohistochemical results or application of chemotherapy. Univ", "wever, the levels of a proliferation marker (Ki-67) and inflammatory cytokine markers, includin"], "order_basis": "paper_text_order:1058", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["icillin/streptomycin (Invitrogen, USA). Both cell lines were maintained in an incubator at 37 °C with 5% CO2. Statis", "purchased from ATCC (Manassas, VA, USA) and cultured in MCDB105 medium (Zhong Qiao Xin Zhou Biotechn", "nticated Cell Cultures (Shanghai, China) and cultured in RPMI-1640 medium (Zhong Qiao Xin Zhou Biotec"], "order_basis": "paper_text_order:7565", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To identify differentially expressed genes (DEGs), we used the FindMarkers function with two-sided unpaired Wilcoxon tests, and p values were adjusted following the Benjamin & Hochberg protocol."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}