Identification of core genes in the progression of endometrial cancer and cancer cell-derived exosomes by an integrative analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32555395", "kind": "science-record", "revision": 8, "content_hash": "sha256:9fcf4f80e08e3b33377cb4351b00ecb70753b61c4f756f471248e8b6b3dcb594", "created_at": "2026-11-01T15:41:03Z", "updated_at": "2026-11-01T22:44:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of core genes in the progression of endometrial cancer and cancer cell-derived exosomes by an integrative analysis.", "doi": "10.1038/s41598-020-66872-3", "pmid": "32555395", "authors": ["Shuang Shi", "Qiang Tan", "Fuqiang Feng", "Heping Huang", "Jingjie Liang", "Dingren Cao", "Zhengguang Wang"], "journal": "Scientific reports", "year": 2020, "abstract": "Endometrial cancer is one of the most prevalent tumors of the female reproductive system causing serious health effects to women worldwide. Although numerous studies, including analysis of gene expression profile and cellular microenvironment have been reported in this field, pathogenesis of this disease remains unclear. In this study, we performed a system bioinformatics analysis of endometrial cancer using the Gene Expression Omnibus (GEO) datasets (GSE17025, GSE63678, and GSE115810) to identify the core genes. In addition, exosomes derived from endometrial cancer cells were also isolated and identified. First, we analyzed the differentially expressed genes (DEGs) between endometrial cancer tissues and normal tissues in clinic samples. We found that HAND2-AS1, PEG3, OGN, SFRP4, and OSR2 were co-expressed across all 3 datasets. Pathways analysis showed that several pathways associated with endometrial cancer, including \"p53 signaling pathway\", \"Glutathione metabolism\", \"Cell cycle\", and etc. Next, we selected DEGs with highly significant fold change and co-expressed across the 3 datasets and validated them in the TCGA database using Gene Expression Profiling Interactive Analysis (GEPIA). Finally, we performed a survival analysis and identified four genes (TOP2A, ASPM, EFEMP1, and FOXL2) that play key roles in endometrial cancer. We found up-regulation of TOP2A and ASPM in endometrial cancer tissues or cells, while EFEMP1 and FOXL2 were down-regulated. Furthermore, we isolated exosomes from the culturing supernatants of endometrial cancer cells (Ishikawa and HEC-1-A) and found that miR-133a, which regulates expression of FOXL2, were present in exosomes and that they could be delivered to normal endometrial cells. The common DEGs, pathways, and exosomal miRNAs identified in this study might play an important role in progression as well as diagnosis of endometrial cancer. In conclusion, our results provide insights into the pathogenesis and risk assessment of endometrial cancer. Even so, further studies are required to elucidate on the precise mechanism of action of these genes in endometrial cancer.", "claims": [{"id": "claim-method", "statement": "The analysis was performed using limma package at cut off values |log FC | > 1.0 and Adjust P value value <0.05 in these three datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32555395", "locator": "sections[14] \"Identification of differentially expressed genes\" paragraph 2", "quote": "The analysis was performed using limma package at cut off values |log FC | > 1.0 and Adjust P value value <0.05 in these three datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available in GEO at https://www.ncbi.nlm.nih.gov/geo/. These data were derived from the following resources available in the public domain: GSE17025, GSE63678 and GSE115810.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32555395", "locator": "sections[21] \"Data availibility\" paragraph 2", "quote": "The data that support the findings of this study are available in GEO at https://www.ncbi.nlm.nih.gov/geo/. These data were derived from the following resources available in the public domain: GSE17025, GSE63678 and GSE115810."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:32555395"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32555395", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-020-66872-3", "sha256": "sha256:6d97fd64145f89091d87851813287fb1edaf0ae6f0ca5aaefe79586771137b70", "bytes": 46804, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-020-66872-3", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7299953", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:32555395:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c25c4d2dc4c5cb5abbaeb01ad9c33c0a51f53fa426178de4ad2a493b8b1b69d1", "bytes": 950, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab2", "version": null, "note": "Top 10 differentially expressed genes in GSE63678.", "structure": {"pmcid": "PMC7299953", "section_index": 3, "section_title": "Identification of DEGs in endometrial cancer", "row_count": 11, "column_count": 5}, "table": {"label": "Table 2", "caption": "Top 10 differentially expressed genes in GSE63678.", "rows": [["Rank", "Probe set ID", "Gene symbol", "Description", "Regulation"], ["1", "209242_at", "PEG3", "paternally expressed 3", "Down-regulation"], ["2", "219791_s_at", "HAND2-AS1", "HAND2 antisense RNA 1", "Down-regulation"], ["3", "206067_s_at", "WT1", "WT1 transcription factor", "Down-regulation"], ["4", "205433_at", "BCHE", "butyrylcholinesterase", "Down-regulation"], ["5", "218730_s_at", "OGN", "osteoglycin", "Down-regulation"], ["6", "204653_at", "TFAP2A", "transcription factor AP-2 alpha", "Up-regulation"], ["7", "201839_s_at", "EPCAM", "epithelial cell adhesion molecule", "Up-regulation"], ["8", "201596_x_at", "KRT18", "keratin 18", "Up-regulation"], ["9", "219148_at", "PBK", "PDZ binding kinase", "Up-regulation"], ["10", "204580_at", "MMP12", "matrix metallopeptidase 12", "Up-regulation"]], "row_count": 11, "column_count": 5, "numeric_cells": 27, "header_rows": 1, "locator": "section[3]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:32555395:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ba71548dece57e308a01fe9503394f0c60b0023ba230a7f97d5e0518b758f774", "bytes": 974, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[2]#Tab1", "version": null, "note": "Top 10 differentially expressed genes in GSE17025.", "structure": {"pmcid": "PMC7299953", "section_index": 3, "section_title": "Identification of DEGs in endometrial cancer", "row_count": 11, "column_count": 5}, "table": {"label": "Table 1", "caption": "Top 10 differentially expressed genes in GSE17025.", "rows": [["Rank", "Probe set ID", "Gene symbol", "Description", "Regulation"], ["1", "202768_at", "FOSB", "FBJ osteosarcoma oncogene B", "Down-regulation"], ["2", "206622_at", "TRH", "thyrotropin releasing hormone", "Down-regulation"], ["3", "219791_s_at", "HAND2-AS1", "HAND2 antisense RNA 1", "Down-regulation"], ["4", "206228_at", "PAX2", "paired box 2", "Down-regulation"], ["5", "209242_at", "PEG3", "paternally expressed 3", "Down-regulation"], ["6", "201291_s_at", "TOP2A", "DNA topoisomerase II alpha", "Up-regulation"], ["7", "1553655_at", "CDC20B", "cell division cycle 20B", "Up-regulation"], ["8", "219918_s_at", "ASPM", "abnormal spindle microtubule assembly", "Up-regulation"], ["9", "202018_s_at", "LTF", "lactotransferrin", "Up-regulation"], ["10", "205476_at", "CCL20", "C-C motif chemokine ligand 20", "Up-regulation"]], "row_count": 11, "column_count": 5, "numeric_cells": 27, "header_rows": 1, "locator": "section[3]/table-wrap[2]#Tab1"}}, {"id": "asset:table:pmid:32555395:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:de40bbb3660b773cc2b40a37d8995b85ff899527d6dcab9cb4da6dfe103ae1fb", "bytes": 993, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[3]#Tab3", "version": null, "note": "Top 10 differentially expressed genes in GSE115810.", "structure": {"pmcid": "PMC7299953", "section_index": 3, "section_title": "Identification of DEGs in endometrial cancer", "row_count": 11, "column_count": 5}, "table": {"label": "Table 3", "caption": "Top 10 differentially expressed genes in GSE115810.", "rows": [["Rank", "Probe set ID", "Gene symbol", "Description", "Regulation"], ["1", "204051_s_at", "SFRP4", "secreted frizzled related protein 4", "Down-regulation"], ["2", "219791_s_at", "HAND2-AS1", "HAND2 antisense RNA 1", "Down-regulation"], ["3", "220102_at", "FOXL2", "forkhead box L2", "Down-regulation"], ["4", "201842_s_at", "EFEMP1", "EGF containing fibulin extracellular matrix protein 1", "Down-regulation"], ["5", "206637_at", "P2RY14", "purinergic receptor P2Y14", "Down-regulation"], ["6", "201195_s_at", "SLC7A5", "solute carrier family 7 member 5", "Up-regulation"], ["7", "202357_s_at", "CFB", "complement factor B", "Up-regulation"], ["8", "209875_s_at", "SPP1", "secreted phosphoprotein 1", "Up-regulation"], ["9", "204846_at", "CP", "ceruloplasmin", "Up-regulation"], ["10", "204623_at", "TFF3", "trefoil factor 3", "Up-regulation"]], "row_count": 11, "column_count": 5, "numeric_cells": 28, "header_rows": 1, "locator": "section[3]/table-wrap[3]#Tab3"}}, {"id": "asset:table:pmid:32555395:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ec435786b6e982bc303f47e32df1348e81c3d9df792ed70cbac0022dd3432a47", "bytes": 1086, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#Tab4", "version": null, "note": "Top 10 pathways in pathway relation network of the 3 datasets (GSE17025, GSE63678 and GSE115810).", "structure": {"pmcid": "PMC7299953", "section_index": 5, "section_title": "Signaling pathway enrichment analysis", "row_count": 11, "column_count": 4}, "table": {"label": "Table 4", "caption": "Top 10 pathways in pathway relation network of the 3 datasets (GSE17025, GSE63678 and GSE115810).", "rows": [["Rank", "GSE17025", "GSE63678", "GSE115810"], ["1", "Cell cycle", "Cell cycle", "ECM-receptor interaction"], ["2", "Leukocyte transendothelial migration", "p53 signaling pathway", "PI3K-Akt signaling pathway"], ["3", "PPAR signaling pathway", "Oocyte meiosis", "Focal adhesion"], ["4", "Pathways in cancer", "Proteoglycans in cancer", "Pathways in cancer"], ["5", "Glutathione metabolism", "Progesterone-mediated oocyte maturation", "Melanoma"], ["6", "p53 signaling pathway", "Melanoma", "Protein digestion and absorption"], ["7", "ECM-receptor interaction", "Mineral absorption", "Cell adhesion molecules (CAMs)"], ["8", "Bile secretion", "Biosynthesis of antibiotics", "MAPK signaling pathway"], ["9", "Progesterone-mediated oocyte maturation", "Prostate cancer", "Amoebiasis"], ["10", "Chemokine signaling pathway", "Pathways in cancer", "Complement and coagulation cascades"]], "row_count": 11, "column_count": 4, "numeric_cells": 15, "header_rows": 1, "locator": "section[5]/table-wrap[1]#Tab4"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The analysis was performed using limma package at cut off values |log FC | > 1.0 and Adjust P value value <0.05 in these three datasets."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["The data that support the findings of this study are available in GEO at https://www.ncbi.nlm.nih.gov/geo/. These data were derived from the following resources available in the public domain: GSE17025, GSE63678 and GSE115810."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:32555395", "asset:table:pmid:32555395:1", "asset:table:pmid:32555395:2", "asset:table:pmid:32555395:3", "asset:table:pmid:32555395:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:04:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 36912, "completion_tokens": 1621, "cached_tokens": 792}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:32555395", "type": "paper", "label": "pmid:32555395"}, {"id": "source:pmid:32555395", "type": "manuscript", "label": "PMID 32555395 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32555395", "type": "paper", "label": "pmid:32555395"}, {"id": "source:pmid:32555395", "type": "manuscript", "label": "PMID 32555395 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32555395", "type": "extraction", "used": ["source:pmid:32555395"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:32555395", "parent_hash": "sha256:68f04e70c6b5986cd5858a452bf52d4830b399c257d55d4779d72b1081f0f327", "fork_of": null, "generation": 7}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"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": ["ium supplemented with 10% FBS. while HEC-1-A cell lines were cultured in McCOY’s 5 A (SIGMA) supplemented with 10%", ", China). Ishikawa and 4003 cells lines were cultured in DMEM (Gibco) culture medium supplemented wit", "with 10% FBS. while HEC-1-A cell lines were cultured in McCOY’s 5 A (SIGMA) supplemented with 10% FB"], "order_basis": "paper_text_order:4975", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The analysis was performed using limma package at cut off values |log FC | > 1.0 and Adjust P value value <0.05 in these three datasets."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}