COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33867982", "kind": "science-record", "revision": 6, "content_hash": "sha256:212c7e007ad46bcf181df68dddafb7c413218d2a8734845033d6dc06e963d338", "created_at": "2026-11-01T15:41:32Z", "updated_at": "2026-11-01T21:25:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis.", "doi": "10.3389/fphar.2021.619732", "pmid": "33867982", "authors": ["Zewen Chu", "Xin Shi", "Gaoyang Chen", "Xuejun He", "Yayun Qian", "Haibo Wang", "Li Tao", "Yanqing Liu", "Wei Jiang", "Jue Chen"], "journal": "Frontiers in pharmacology", "year": 2021, "abstract": "New strategies and drugs are urgently needed to improve the treatment of hepatocellular carcinoma (HCC). Vasculogenic mimicry (VM) has been elucidated being associated with the progression of HCC and anti-VM could be a promising strategy. Celastrus orbiculatu s extract (COE), a mixture of 26 compounds isolated from the Chinese Herb Celastrus Orbiculatus Vine, has been elucidated to be able to disrupt VM formation in HCC. This study aims to dissect and identify the potential targets of COE on anti-VM formation both in vitro and in vivo that are distinct from our previous study. Proteomics analysis was used to identify differential proteins in HCC cells treated with or without COE (Data are available via ProteomeXchange with identifier PXD022203). Cells invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation in vitro. RT-PCR and Western Blot were used to examine changes of mRNA and protein respectively. Clinical resected samples were applied to confirm association between VM formation and identified targets. Subcutaneous xenograft tumor model was established to observe tumor growth and VM formation in vivo. PAS-CD34 dual staining was used to detect VM in vivo. A total of 194 proteins were identified to be differentially expressed in HCC cells treated with or without COE. In the 93 down-regulated proteins EphA2 stood out to be regulated on both RNA and protein level. Disruption EphA2 using COE or NVP inhibited VM formation and decreased VM associated biomarkers. In xenograft mouse model, COE inhibited tumor growth and VM formation via down-regulating EphA2. Taken together, our results indicate that COE could be used in HCC treatment because of its promising anti-VM effect.", "claims": [{"id": "claim-method", "statement": "Continuous variables were expressed as the means ± SD and were compared between groups by using the Student’s t-test. Categorical variables were compared by using the Chi-Square test. The Mann–Whitney test was for non-normal distributive data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33867982", "locator": "sections[19] \"Statistical Analysis\" paragraph 2", "quote": "Continuous variables were expressed as the means ± SD and were compared between groups by using the Student’s t-test. Categorical variables were compared by using the Chi-Square test. The Mann–Whitney test was for non-normal distributive data."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The name of the repository and accession number can be found below: ProteomeXchange Consortium via the PRIDE [1] partner repository, http://www.proteomexchange.org/, PXD022203.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33867982", "locator": "sections[29] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The name of the repository and accession number can be found below: ProteomeXchange Consortium via the PRIDE [1] partner repository, http://www.proteomexchange.org/, PXD022203."}], "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:33867982"], "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:33867982", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2021.619732", "sha256": "sha256:0b912ef35ddfd436f939432988869a7325d5fd2a822d1eb4fa10848da048ce2f", "bytes": 53256, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2021.619732", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8044863", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33867982:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:32aa750bcae55cf9952427ca41ef59e425b9ad11ffe4e4b5848f1cf1aa5bd7ed", "bytes": 1190, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T1", "version": null, "note": "The primers.", "structure": {"pmcid": "PMC8044863", "section_index": 13, "section_title": "Reverse Transcription PCR", "row_count": 17, "column_count": 3}, "table": {"label": "TABLE 1", "caption": "The primers.", "rows": [["Primer", "Sequence of primer (5′→3′)", "amplification (bp)"], ["h-LIX1L-F", "CAA​GGG​CAA​ATC​AAT​GTT​GGA​G", "133"], ["h-LIX1L-R", "CCG​GTG​CGA​ATA​ATG​AGC​CA"], ["h-HIST2H2BE-F", "ATG​CCT​GAA​CCG​GCA​AAA​TC", "287"], ["h-HIST2H2BE-R", "TGG​ATC​TCG​CGG​GAT​GTG​AT"], ["h-MYO1F-F", "CAA​GCA​GAT​GCC​CTA​CTT​CAC", "120"], ["h-MYO1F-R", "TCG​ATA​AGC​ATG​TTC​CGG​TAC​A"], ["h-SBF2-F", "TCA​TCG​TGG​TAG​GCT​ATG​ACC", "133"], ["h-SBF2-R", "CCA​GGC​TGA​CAA​AAC​AAC​TCA"], ["h-HOMER1-F", "CCG​GGC​AAA​CAC​CGT​TTA​TG", "100"], ["h-HOMER1-R", "TGC​TAG​TCG​AGC​AGC​TTC​TTT​A"], ["h-GAPDH-F", "GGA​GCG​AGA​TCC​CTC​CAA​AAT", "197"], ["h-GAPDH-R", "GGC​TGT​TGT​CAT​ACT​TCT​CAT​GG"], ["h-COX6A1-F", "AGT​TGG​TGT​GTC​CTC​GGT​TTC", "117"], ["h-COX6A1-R", "GTG​AGA​GTC​TTC​CAC​ATG​CGA"], ["h-EphA2-F", "TGG​CTC​ACA​CAC​CCG​TAT​G", "102"], ["h-EphA2-R", "GTC​GCC​AGA​CAT​CAC​GTT​G"]], "row_count": 17, "column_count": 3, "numeric_cells": 9, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33867982:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ab43f0736501da0b8a008f4447f5d43b88ab21fef6d741f2c28d180b650b22d5", "bytes": 498, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#T2", "version": null, "note": "The antibodies.", "structure": {"pmcid": "PMC8044863", "section_index": 14, "section_title": "Western Blot Analysis", "row_count": 7, "column_count": 5}, "table": {"label": "TABLE 2", "caption": "The antibodies.", "rows": [["Name", "Mol. Wt (KD)", "Dilution", "Company", "Catalogue number"], ["VE-cadherin", "87", "1/1,000", "abcam", "ab33168"], ["MMP2", "74", "1/1,000", "abcam", "ab97779"], ["MMP9", "92", "1/1,000", "abcam", "ab38898"], ["E-cadherin", "130", "1/1,000", "proteintech", "20874-1-AP"], ["Twist1", "21", "1/50", "abcam", "ab50887"], ["EphA2", "125", "1/1,000", "cst", "6997"]], "row_count": 7, "column_count": 5, "numeric_cells": 18, "header_rows": 1, "locator": "section[14]/table-wrap[1]#T2"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Continuous variables were expressed as the means ± SD and were compared between groups by using the Student’s t-test. Categorical variables were compared by using the Chi-Square test. The Mann–Whitney test was for non-normal distributive data."}}], "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": ["chi_square_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: chi_square."}, "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 datasets presented in this study can be found in online repositories. The name of the repository and accession number can be found below: ProteomeXchange Consortium via the PRIDE [1] partner repository, http://www.proteomexchange.org/, PXD022203."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["chi_square_test"], "assets": ["source:pmid:33867982", "asset:table:pmid:33867982:1", "asset:table:pmid:33867982:2"], "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": "2026-10-31T19:31:34Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 45096, "completion_tokens": 1454, "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:33867982", "type": "paper", "label": "pmid:33867982"}, {"id": "source:pmid:33867982", "type": "manuscript", "label": "PMID 33867982 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33867982", "type": "paper", "label": "pmid:33867982"}, {"id": "source:pmid:33867982", "type": "manuscript", "label": "PMID 33867982 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33867982", "type": "extraction", "used": ["source:pmid:33867982"], "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:33867982", "parent_hash": "sha256:d32008b63a777536b5e370176eeb732f50b13d2155e6bff57124e2acec00f2c8", "fork_of": null, "generation": 5}, "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": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["eased VM associated biomarkers. In xenograft mouse model, COE inhibited tumor growth and VM formation", "f COE on anti-VM formation both in vitro and in vivo that are distinct from our previous study. P", "hed to observe tumor growth and VM formation in vivo. PAS-CD34 dual staining was used to detect V", "PAS-CD34 dual staining was used to detect VM in vivo. A total of 194 proteins were identified to"], "order_basis": "paper_text_order:611", "id": "assay:1"}, {"role": "data_generation", "definition_id": "clinical_trial", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["identify differential proteins in HCC cells treated with or without COE (Data are available via ProteomeXchange", "to be differentially expressed in HCC cells treated with or without COE. In the 93 down-regulated proteins EphA2"], "order_basis": "paper_text_order:739", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["dition for VM formation in vitro. RT-PCR and Western Blot were used to examine changes of mRNA and pro"], "order_basis": "paper_text_order:972", "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": 0.77, "evidence": ["tocellular carcinoma cell lines MHCC97-H and HepG2 were purchased from Zhong Qiao Xin Zhou Biot"], "order_basis": "paper_text_order:1922", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["previous report (Cho et al., 2020). For the immunofluorescence analysis, paraffin-embedded human HCC sectio"], "order_basis": "paper_text_order:3921", "id": "assay:5"}, {"role": "data_generation", "definition_id": "cell_imaging", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["lls were detected by confocal laser scanning microscopy (Nikon Eclipse TE2000-U). This study was app"], "order_basis": "paper_text_order:4168", "id": "assay:6"}, {"role": "analysis", "definition_id": "contingency_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["chi_square_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Continuous variables were expressed as the means ± SD and were compared between groups by using the Student’s t-test. Categorical variables were compared by using the Chi-Square test. The Mann–Whitney test was for non-normal distributive data."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}