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pmid:33324095

Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer.

Jiafa Wu · Dongping Luo · Shengnan Li

Breast cancer (Dove Medical Press) · 2020 doi:10.2147/BCTT.S284076

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33324095
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science-record
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sha256:ea4094f791b0dd69d321bc78f3f487976db4a72b76a110bb454565c548c42e4e
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2026-11-01T15:41:19Z
updated_at
2026-11-01T22:45:48Z
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paper object · 10 fields
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title
Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer.
doi
10.2147/BCTT.S284076
pmid
33324095
authors array · 3 items
[0]
Jiafa Wu
[1]
Dongping Luo
[2]
Shengnan Li
journal
Breast cancer (Dove Medical Press)
year
2020
abstract
PURPOSE: The compound traditional Chinese medicine Xihuang pill (XHP) has been adopted to treat breast cancer (BC) for centuries, but its specific mechanism of action is unclear. MATERIALS AND METHODS: The active ingredients and related targets of XHP were screened using the TCMSP and TCMID databases. GSE139038 was downloaded from the GEO database, and differentially expressed genes (DEGs) were analyzed. The intersection of targets and DEGs were chosen to build an ingredients-target genes network. Protein-protein interaction network construction and functional enrichment analysis of target genes were conducted. RESULTS: A PPI network of 37 targets was constructed, and seven core nodes (FOS, MYC, JUN, PPARG, MMP9, PTGS2, SERPINE1) were identified. Functional enrichment analysis revealed that the aforementioned targets were mainly enriched in the IL-17, toll-like receptor, and tumor necrosis factor signaling pathways, which are deeply involved in the inflammatory microenvironment of tumors. CONCLUSION: This network pharmacology study indicated that XHP can inhibit the development of BC by targeting a variety of proteins and signaling pathways involved in the inflammatory microenvironment.
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R packages (“limma” and “pheatmap”) were used to analyze GSE139038. DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1.
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methodological
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sections[3] "Identification of the Differentially Expressed Genes (DEGs) of BC" paragraph 2
quote
R packages (“limma” and “pheatmap”) were used to analyze GSE139038. DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1.
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GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions.
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sections[3] "Identification of the Differentially Expressed Genes (DEGs) of BC" paragraph 2
quote
GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions.
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GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions.
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Gene expression profiling in paired normal, apparently normal and breast tumour tissues
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Top 10 Genes in the Network Ranked by Degree
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R packages (“limma” and “pheatmap”) were used to analyze GSE139038. DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1.
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GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions.
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R packages (“limma” and “pheatmap”) were used to analyze GSE139038. DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1.
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assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33324095", "kind": "science-record", "revision": 9, "content_hash": "sha256:ea4094f791b0dd69d321bc78f3f487976db4a72b76a110bb454565c548c42e4e", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T22:45:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer.", "doi": "10.2147/BCTT.S284076", "pmid": "33324095", "authors": ["Jiafa Wu", "Dongping Luo", "Shengnan Li"], "journal": "Breast cancer (Dove Medical Press)", "year": 2020, "abstract": "PURPOSE: The compound traditional Chinese medicine Xihuang pill (XHP) has been adopted to treat breast cancer (BC) for centuries, but its specific mechanism of action is unclear.\nMATERIALS AND METHODS: The active ingredients and related targets of XHP were screened using the TCMSP and TCMID databases. GSE139038 was downloaded from the GEO database, and differentially expressed genes (DEGs) were analyzed. The intersection of targets and DEGs were chosen to build an ingredients-target genes network. Protein-protein interaction network construction and functional enrichment analysis of target genes were conducted.\nRESULTS: A PPI network of 37 targets was constructed, and seven core nodes (FOS, MYC, JUN, PPARG, MMP9, PTGS2, SERPINE1) were identified. Functional enrichment analysis revealed that the aforementioned targets were mainly enriched in the IL-17, toll-like receptor, and tumor necrosis factor signaling pathways, which are deeply involved in the inflammatory microenvironment of tumors.\nCONCLUSION: This network pharmacology study indicated that XHP can inhibit the development of BC by targeting a variety of proteins and signaling pathways involved in the inflammatory microenvironment.", "claims": [{"id": "claim-method", "statement": "R packages (“limma” and “pheatmap”) were used to analyze GSE139038. DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33324095", "locator": "sections[3] \"Identification of the Differentially Expressed Genes (DEGs) of BC\" paragraph 2", "quote": "R packages (“limma” and “pheatmap”) were used to analyze GSE139038. DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33324095", "locator": "sections[3] \"Identification of the Differentially Expressed Genes (DEGs) of BC\" paragraph 2", "quote": "GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:33324095"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE139038"], "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": ["data:geo:GSE139038"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33324095", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/BCTT.S284076", "sha256": "sha256:ae22dea5791d30faeeb4c0bebeaa8af634d62b2bef2ac5c31692fc83397367ec", "bytes": 26349, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/BCTT.S284076", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7733446", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE139038", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139038", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE139038", "version": null, "note": "GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM4127905", "GSM4127906", "GSM4127907", "GSM4127908", "GSM4127909", "GSM4127910", "GSM4127911", "GSM4127912", "GSM4127913", "GSM4127914", "GSM4127915", "GSM4127916", "GSM4127917", "GSM4127918", "GSM4127919", "GSM4127920", "GSM4127921", "GSM4127922", "GSM4127923", "GSM4127924", "GSM4127925", "GSM4127926", "GSM4127927", "GSM4127928", "GSM4127929", "GSM4127930", "GSM4127931", "GSM4127932", "GSM4127933", "GSM4127934", "GSM4127935", "GSM4127936", "GSM4127937", "GSM4127938", "GSM4127939", "GSM4127940", "GSM4127941", "GSM4127942", "GSM4127943", "GSM4127944", "GSM4127945", "GSM4127946", "GSM4127947", "GSM4127948", "GSM4127949", "GSM4127950", "GSM4127951", "GSM4127952", 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"reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#t0002", "version": null, "note": "Top 10 Genes in the Network Ranked by Betweenness", "structure": {"pmcid": "PMC7733446", "section_index": 11, "section_title": "PPI Network Construction", "row_count": 11, "column_count": 3}, "table": {"label": "Table 2", "caption": "Top 10 Genes in the Network Ranked by Betweenness", "rows": [["Rank", "Name", "Score"], ["1", "FOS", "167.0219"], ["2", "MYC", "161.2401"], ["3", "JUN", "138.6833"], ["4", "PPARG", "132.3155"], ["5", "MMP9", "98.98592"], ["6", "PTGS2", "88.6258"], ["7", "SERPINE1", "81.44932"], ["8", "NR3C1", "72.60143"], ["9", "GSTM2", "47.24919"], ["10", "GSTA2", "46.27636"]], "row_count": 11, "column_count": 3, "numeric_cells": 20, "header_rows": 1, "locator": "section[11]/table-wrap[2]#t0002"}}, {"id": "asset:table:pmid:33324095:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, 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DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Protein-protein interaction"}}], "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "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": "R1", "reachable": true, "accessions": ["GSE139038"], "resolved_accessions": ["GSE139038"], "statements": ["GSE139038 was downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE139038 was based on the GPL27630 Print_1437 platform. GSE139038 contains 65 samples including 41 breast tumors (24 early stage, 17 locally advanced), 18 adjacent normal tissues (paired normal), and 6 apparently normal tissues from breasts in patients who underwent surgery for non-malignant conditions."], "basis": "The paper names GSE139038 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:33324095", "data:geo:GSE139038", "asset:table:pmid:33324095:1", "asset:table:pmid:33324095:2", "asset:table:pmid:33324095:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE139038"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:25:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 22585, "completion_tokens": 667, "cached_tokens": 7680}}, "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:33324095", "type": "paper", "label": "pmid:33324095"}, {"id": "source:pmid:33324095", "type": "manuscript", "label": "PMID 33324095 full text"}, {"id": "data:geo:GSE139038", "type": "dataset", "label": "GEO GSE139038"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33324095", "type": "paper", "label": "pmid:33324095"}, {"id": "source:pmid:33324095", "type": "manuscript", "label": "PMID 33324095 full text"}, {"id": "data:geo:GSE139038", "type": "dataset", "label": "GEO GSE139038"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33324095", "type": "extraction", "used": ["source:pmid:33324095"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE139038", "type": "accession_resolution", "used": ["data:geo:GSE139038"], "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:33324095", "parent_hash": "sha256:ebf8ed8dd1d10a89da6f82e3ef5a01052c9620d904cc4ea4050bfef535dfb85f", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE139038 licence not read", "asset:data:geo:GSE139038 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["R packages (“limma” and “pheatmap”) were used to analyze GSE139038. DEGs between normal tissue and breast tumors were detected on the basis of the criteria adjusted P-value < 0.05 and |logFC| > 1."], "order_basis": "analysis_only", "id": "assay:1"}]}