Identification of UBE2I as a Novel Biomarker in ccRCC Based on a Large-Scale CRISPR-Cas9 Screening Database and Immunohistochemistry.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35211510", "kind": "science-record", "revision": 4, "content_hash": "sha256:f87862a19899c005b96fcb8fa41e5c35d7b703efb2c6d9ad2e3cda58897949b6", "created_at": "2026-11-01T17:36:58Z", "updated_at": "2026-11-01T22:05:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of UBE2I as a Novel Biomarker in ccRCC Based on a Large-Scale CRISPR-Cas9 Screening Database and Immunohistochemistry.", "doi": "10.3389/fmolb.2022.813428", "pmid": "35211510", "authors": ["Feng Li", "Li Lai", "Zhijie You", "Hui Cheng", "Guodong Guo", "Chenchen Tang", "Luyun Xu", "Hongxia Liu", "Wenting Zhong", "Youyu Lin", "Qingshui Wang", "Yao Lin", "Yongbao Wei"], "journal": "Frontiers in molecular biosciences", "year": 2022, "abstract": "Background: The genome-wide CRISPR-cas9 dropout screening has emerged as an outstanding approach for characterization of driver genes of tumor growth. The present study aims to investigate core genes related to clear cell renal cell carcinoma (ccRCC) cell viability by analyzing the CRISPR-cas9 screening database DepMap, which may provide a novel target in ccRCC therapy. Methods: Candidate genes related to ccRCC cell viability by CRISPR-cas9 screening from DepMap and genes differentially expressed between ccRCC tissues and normal tissues from TCGA were overlapped. Weighted gene coexpression network analysis, pathway enrichment analysis, and protein-protein interaction network analysis were applied for the overlapped genes. The least absolute shrinkage and selection operator (LASSO) regression was used to construct a signature to predict the overall survival (OS) of ccRCC patients and validated in the International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. Core protein expression was determined using immunohistochemistry in 40 cases of ccRCC patients. Results: A total of 485 essential genes in the DepMap database were identified and overlapped with differentially expressed genes in the TCGA database, which were enriched in the cell cycle pathway. A total of four genes, including UBE2I, NCAPG, NUP93, and TOP2A, were included in the gene signature based on LASSO regression. The high-risk score of ccRCC patients showed worse OS compared with these low-risk patients in the ICGC and E-MTAB-1980 validation cohort. UBE2I was screened out as a key gene. The immunohistochemistry indicated UBE2I protein was highly expressed in ccRCC tissues, and a high-level nuclear translocation of UBE2I occurs in ccRCC. Based on the area under the curve (AUC) values, nuclear UBE2I had the best diagnostic power (AUC = 1). Meanwhile, the knockdown of UBE2I can inhibit the proliferation of ccRCC cells. Conclusion: UBE2I, identified by CRISPR-cas9 screening, was a core gene-regulating ccRCC cell viability, which accumulated in the nucleus and acted as a potential novel promising diagnostic biomarker for ccRCC patients. Blocking the nuclear translocation of UBE2I may have potential therapeutic value with ccRCC patients.", "claims": [{"id": "claim-method", "statement": "Further on, to assess the capacity of the UBE2I assay to differentiate between ccRCC and normal samples, receiver operating characteristic (ROC) curve analyses were performed, using the IHC data of the UBE2I nucleus as an independent classifier.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35211510", "locator": "sections[20] \"Expression of UBE2I in Clinical Specimens\" paragraph 4", "quote": "Further on, to assess the capacity of the UBE2I assay to differentiate between ccRCC and normal samples, receiver operating characteristic (ROC) curve analyses were performed, using the IHC data of the UBE2I nucleus as an independent classifier."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35211510", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Based on the area under the curve (AUC) values, nuclear UBE2I had the best diagnostic power (AUC = 1).", "kind": "quantitative", "target": {"value": 1.0, "unit": "auc", "tolerance": null, "source": "Based on the area under the curve (AUC) values, nuclear UBE2I had the best diagnostic power (AUC = 1)."}, "evidence": [{"asset": "source:pmid:35211510", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Based on the area under the curve (AUC) values, nuclear UBE2I had the best diagnostic power (AUC = 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Based on the area under the curve (AUC) values, nuclear UBE2I had the best diagnostic power (AUC = 1).", "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:35211510"], "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:E-MTAB-1980"], "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:E-MTAB-1980"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35211510", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2022.813428", "sha256": "sha256:3c2ee6e9d900a0fc65c9ade752517a8a1db22b778a941e02f21cb42b2857536f", "bytes": 33851, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2022.813428", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8861443", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:E-MTAB-1980", "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=E-MTAB-1980", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "E-MTAB-1980", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-10-31T18:28:57Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:E-MTAB-1980 not downloaded", "asset:data:geo:E-MTAB-1980 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-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"}}, {"id": "method-3", "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"}}, {"id": "method-4", "family": null, "specific": null, "label": "receiver operating characteristic (ROC) curve analyses", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Further on, to assess the capacity of the UBE2I assay to differentiate between ccRCC and normal samples, receiver operating characteristic (ROC) curve analyses were performed, using the IHC data of the UBE2I nucleus as an independent classifier."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 1.0, "unit": "auc", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": ["method.reader_named_unmapped"]}, "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": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "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": ["E-MTAB-1980"], "resolved_accessions": ["E-MTAB-1980"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names E-MTAB-1980 in ArrayExpress and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:35211510", "data:geo:E-MTAB-1980"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:E-MTAB-1980"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:35:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10175, "completion_tokens": 2037, "cached_tokens": 128}}, "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:35211510", "type": "paper", "label": "pmid:35211510"}, {"id": "source:pmid:35211510", "type": "manuscript", "label": "PMID 35211510 full text"}, {"id": "data:geo:E-MTAB-1980", "type": "dataset", "label": "GEO E-MTAB-1980"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35211510", "type": "paper", "label": "pmid:35211510"}, {"id": "source:pmid:35211510", "type": "manuscript", "label": "PMID 35211510 full text"}, {"id": "data:geo:E-MTAB-1980", "type": "dataset", "label": "GEO E-MTAB-1980"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35211510", "type": "extraction", "used": ["source:pmid:35211510"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-E-MTAB-1980", "type": "accession_resolution", "used": ["data:geo:E-MTAB-1980"], "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:35211510", "parent_hash": "sha256:08948b535fc57f5595a0d07651fe57eb9a93fc61eaf58ce90225d30d22893487", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:E-MTAB-1980 licence not read", "asset:data:geo:E-MTAB-1980 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["el Biomarker in ccRCC Based on a Large-Scale CRISPR-Cas9 Screening Database and Immunohistochemi", "t diagnostic power (AUC = 1). Meanwhile, the knockdown of UBE2I can inhibit the proliferation of cc", "Background: The genome-wide CRISPR-cas9 dropout screening has emerged as an out", "noma (ccRCC) cell viability by analyzing the CRISPR-cas9 screening database DepMap, which may pr"], "order_basis": "paper_text_order:32", "id": "assay:1"}, {"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": ["rge-Scale CRISPR-Cas9 Screening Database and Immunohistochemistry.", "Core protein expression was determined using immunohistochemistry in 40 cases of ccRCC patients. Results: A to", "t. UBE2I was screened out as a key gene. The immunohistochemistry indicated UBE2I protein was highly expressed"], "order_basis": "paper_text_order:67", "id": "assay:2"}, {"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": ["98 cells and 786-O cells were, respectively, cultured in MEM Alpha medium (Gibco by Life Technologies"], "order_basis": "paper_text_order:2868", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["log-rank"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}