ID1 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Deterioration of Clear Cell Renal Cell Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33178820", "kind": "science-record", "revision": 7, "content_hash": "sha256:c3418de4993281e868158fdf18dca48b7e58f3001c437990f40d4ede2eba1259", "created_at": "2026-11-01T15:41:15Z", "updated_at": "2026-11-01T22:02:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "ID1 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Deterioration of Clear Cell Renal Cell Carcinoma.", "doi": "10.1155/2020/2064582", "pmid": "33178820", "authors": ["Xiangmin Qiu", "Yuping Gu", "Yilu Ni", "Qianyin Li"], "journal": "BioMed research international", "year": 2020, "abstract": "Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers in the world. Our aim is to identify prognostic biomarkers that contribute to the progression of early stage ccRCC and clarify the mechanism. Here, the mRNA microarray expression profile of ccRCC samples was obtained from Gene Expression Omnibus (GEO) (GSE68417). 62 differentially expressed genes (DEGs) were gained by R Studio, including 31 upregulated genes and 31 downregulated genes. Pathway enrichment analysis was performed in DAVID database. Then, the protein-protein interaction network was obtained through STRING database and visualized by Cytoscape. Subsequently, among the network, only inhibitor of DNA Binding 1 (ID1) was significant between low-grade and high-grade ccRCC patients in TCGA data set. After analysis of the corresponding clinical information in R Studio, it is shown that low ID1 expression correlated with poor survival, high probability of tumor metastasis, and relatively high serum calcium. Later, functional enrichment of ID1 in GeneMANIA uncovered that regulating DNA binding is a main characteristic of ID1 in ccRCC, which was validated by Kaplan-Meier curve of ID1 associated genes using KM plotter database and R Studio. Immune infiltration analysis performed by Tumor Immune Estimation Resource (TIMER) revealed that CD8+ T cells and macrophages were prognostic factors. Furthermore, Valproic acid was analyzed to be the most convinced target drug of ID1 identified by Comparative Toxicogenomics Database (CTD). Taken together, ID1, a biomarker of clinical outcome in early stage ccRCC patients, has the potential function of preventing deterioration in ccRCC progression and metastasis.", "claims": [{"id": "claim-method", "statement": "The correlation between ID1 expression and the infiltration level of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells was analyzed using the Spearman correlation test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33178820", "locator": "sections[9] \"2.7. Correlation Analysis of ID1 and Immune Cell Infiltration\" paragraph 2", "quote": "The correlation between ID1 expression and the infiltration level of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells was analyzed using the Spearman correlation test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33178820", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "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:33178820"], "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:GSE68417"], "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:GSE68417"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33178820", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2020/2064582", "sha256": "sha256:b4e953a3086a1c1171f6c87673e7546a94a71c66403ec6a7ff0d2f0267599506", "bytes": 33614, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2020/2064582", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7647745", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE68417", "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=GSE68417", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68417", "version": null, "note": "The data used to support the findings of this study are available from the corresponding author upon request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used to support the findings of this study are available from the corresponding author upon request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1671350", "GSM1671351", "GSM1671352", "GSM1671353", "GSM1671354", "GSM1671355", "GSM1671356", "GSM1671357", "GSM1671358", "GSM1671359", "GSM1671360", "GSM1671361", "GSM1671362", "GSM1671363", "GSM1671364", "GSM1671365", "GSM1671366", "GSM1671367", "GSM1671368", "GSM1671369", "GSM1671370", "GSM1671371", "GSM1671372", "GSM1671373", "GSM1671374", "GSM1671375", "GSM1671376", "GSM1671377", "GSM1671378", "GSM1671379", "GSM1671380", "GSM1671381", "GSM1671382", "GSM1671383", "GSM1671384", "GSM1671385", "GSM1671386", "GSM1671387", "GSM1671388", "GSM1671389", "GSM1671390", "GSM1671391", "GSM1671392", "GSM1671393", "GSM1671394", "GSM1671395", "GSM1671396", "GSM1671397", "GSM1671398"], "sample_count": 49, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression characterization of high and low grade clear cell renal cell carcinoma", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33178820:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:993673940388fc88dac227b0c83fedfe3cfd6d4e50e40b100b4c9a3f54aa717b", "bytes": 1214, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#tab1", "version": null, "note": "KEGG pathway enrichment analysis of upregulated DEGs.", "structure": {"pmcid": "PMC7647745", "section_index": 13, "section_title": "3.2. GO Term and KEGG Analysis of DEGs", "row_count": 15, "column_count": 5}, "table": {"label": "Table 1", "caption": "KEGG pathway enrichment analysis of upregulated DEGs.", "rows": [["ID", "Description", "Gene ratio", "Number of enriched genes", "P value"], ["hsa04015", "Rap1 signaling pathway", "0.25000", "5", "0.00014"], ["hsa04371", "Apelin signaling pathway", "0.20000", "4", "0.00033"], ["hsa04010", "MAPK signaling pathway", "0.25000", "5", "0.00068"], ["hsa05231", "Choline metabolism in cancer", "0.15000", "3", "0.00179"], ["hsa04928", "Parathyroid hormone synthesis, secretion and action", "0.15000", "3", "0.00225"], ["hsa05418", "Fluid shear stress and atherosclerosis", "0.15000", "3", "0.00484"], ["hsa04151", "PI3K-Akt signaling pathway", "0.20000", "4", "0.01074"], ["hsa05031", "Amphetamine addiction", "0.10000", "2", "0.01247"], ["hsa03320", "PPAR signaling pathway", "0.10000", "2", "0.01542"], ["hsa04014", "Ras signaling pathway", "0.15000", "3", "0.01953"], ["hsa05323", "Rheumatoid arthritis", "0.10000", "2", "0.02256"], ["hsa04657", "IL-17 signaling pathway", "0.10000", "2", "0.02302"], ["hsa04925", "Aldosterone synthesis and secretion", "0.10000", "2", "0.02488"], ["hsa04380", "Osteoclast differentiation", "0.10000", "2", "0.04067"]], "row_count": 15, "column_count": 5, "numeric_cells": 57, "header_rows": 1, "locator": "section[13]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:33178820:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6ab2e509dd64c18767bb920aed6f1aa946f2604e3d8e8944cd220a9ee0d78ce1", "bytes": 1200, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#tab2", "version": null, "note": "KEGG pathway enrichment analysis of downregulated DEGs.", "structure": {"pmcid": "PMC7647745", "section_index": 13, "section_title": "3.2. GO Term and KEGG Analysis of DEGs", "row_count": 15, "column_count": 5}, "table": {"label": "Table 2", "caption": "KEGG pathway enrichment analysis of downregulated DEGs.", "rows": [["ID", "Description", "Gene ratio", "Number of enriched genes", "P value"], ["hsa05133", "Pertussis", "0.15789", "3", "0.00074"], ["hsa00770", "Pantothenate and CoA biosynthesis", "0.10526", "2", "0.00091"], ["hsa05322", "Systemic lupus erythematosus", "0.15789", "3", "0.00368"], ["hsa05030", "Cocaine addiction", "0.10526", "2", "0.00599"], ["hsa04720", "Long-term potentiation", "0.10526", "2", "0.01097"], ["hsa05031", "Amphetamine addiction", "0.10526", "2", "0.01129"], ["hsa04610", "Complement and coagulation cascades", "0.10526", "2", "0.01503"], ["hsa05132", "Salmonella infection", "0.10526", "2", "0.01539"], ["hsa05150", "Staphylococcus aureus infection", "0.10526", "2", "0.02171"], ["hsa04061", "Viral protein interaction with cytokine", "0.10526", "2", "0.02344"], ["hsa04064", "NF-kappa B signaling pathway", "0.10526", "2", "0.02432"], ["hsa04620", "Toll-like receptor signaling pathway", "0.10526", "2", "0.02522"], ["hsa04728", "Dopaminergic synapse", "0.10526", "2", "0.03859"], ["hsa00360", "Phenylalanine metabolism", "0.05263", "1", "0.04002"]], "row_count": 15, "column_count": 5, "numeric_cells": 56, "header_rows": 1, "locator": "section[13]/table-wrap[2]#tab2"}}, {"id": "asset:table:pmid:33178820:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c29d580fd7b465626fd94388de2e3de9dffc6b208512eac170f7075344134130", "bytes": 420, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#tab3", "version": null, "note": "Significance of clinical indicators between two groups.", "structure": {"pmcid": "PMC7647745", "section_index": 14, "section_title": "3.3. Discovery of Critical Gene in patient's Survival", "row_count": 7, "column_count": 3}, "table": {"label": "Table 3", "caption": "Significance of clinical indicators between two groups.", "rows": [["Clinical indicators", "P value", "Significance"], ["T (tumor)", "0.414", ""], ["N (nodes)", "0.73", ""], ["M (metastasis)", "0.032", "∗"], ["Lymph nodes", "0.068", ""], ["Serum calcium", "0.021", "∗"], ["Hemoglobin", "0.925", ""]], "row_count": 7, "column_count": 3, "numeric_cells": 6, "header_rows": 1, "locator": "section[14]/table-wrap[1]#tab3"}}, {"id": "asset:table:pmid:33178820:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:783e43466d31fd96d0ca6072bb117fdd61991a7aabb83ce3cdda83f894f49dc4", "bytes": 619, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#tab4", "version": null, "note": "Multivariate Cox analysis of immune cells infiltration.", "structure": {"pmcid": "PMC7647745", "section_index": 16, "section_title": "3.5. ID1 Related to Patients' Immune System", "row_count": 7, "column_count": 6}, "table": {"label": "Table 4", "caption": "Multivariate Cox analysis of immune cells infiltration.", "rows": [["Cell type", "Coef", "HR", "95% CI", "P value", "Sig"], ["B_cell", "-0.600", "0.549", "(0.022, 13.575)", "0.714", ""], ["CD8_Tcell", "-1.741", "0.175", "(0.037, 0.837)", "0.029", "∗"], ["CD4_Tcell", "-0.524", "0.592", "(0.039, 8.902)", "0.705", ""], ["Macrophage", "-2.774", "0.062", "(0.006, 0.647)", "0.020", "∗"], ["Neutrophil", "3.211", "24.809", "(0.389, 1582.755)", "0.130", ""], ["Dendritic", "1.119", "3.062", "(0.517, 18.131)", "0.217", ""]], "row_count": 7, "column_count": 6, "numeric_cells": 25, "header_rows": 1, "locator": "section[16]/table-wrap[1]#tab4"}}], "gaps": ["asset:data:geo:GSE68417 not downloaded", "asset:data:geo:GSE68417 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The correlation between ID1 expression and the infiltration level of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells was analyzed using the Spearman correlation test."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "student t-test"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Log-rank"}}, {"id": "method-5", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}, {"id": "method-6", "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"}}, {"id": "method-7", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pathway enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["spearman_rho"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: spearman."}, "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": ["GSE68417"], "resolved_accessions": ["GSE68417"], "statements": ["The data used to support the findings of this study are available from the corresponding author upon request."], "basis": "The paper names GSE68417 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["spearman_rho"], "assets": ["source:pmid:33178820", "data:geo:GSE68417", "asset:table:pmid:33178820:1", "asset:table:pmid:33178820:2", "asset:table:pmid:33178820:3", "asset:table:pmid:33178820:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE68417"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:24:09Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 28093, "completion_tokens": 2295, "cached_tokens": 785}}, "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:33178820", "type": "paper", "label": "pmid:33178820"}, {"id": "source:pmid:33178820", "type": "manuscript", "label": "PMID 33178820 full text"}, {"id": "data:geo:GSE68417", "type": "dataset", "label": "GEO GSE68417"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33178820", "type": "paper", "label": "pmid:33178820"}, {"id": "source:pmid:33178820", "type": "manuscript", "label": "PMID 33178820 full text"}, {"id": "data:geo:GSE68417", "type": "dataset", "label": "GEO GSE68417"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33178820", "type": "extraction", "used": ["source:pmid:33178820"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE68417", "type": "accession_resolution", "used": ["data:geo:GSE68417"], "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:33178820", "parent_hash": "sha256:bce081c2b38da89515b3e4436bd8702c57fbdc6b650235f2eaa2ea99793b4800", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE68417 licence not read", "asset:data:geo:GSE68417 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["CC and clarify the mechanism. Here, the mRNA microarray expression profile of ccRCC samples was obta"], "order_basis": "paper_text_order:316", "id": "assay:1"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["spearman_rho"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The correlation between ID1 expression and the infiltration level of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells was analyzed using the Spearman correlation test."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}