Identification of ATP1B1, a key copy number driver gene in diffuse large B-cell lymphoma and potential target for drugs.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36388804", "kind": "science-record", "revision": 4, "content_hash": "sha256:e184a1d4d404d592f1e3f34392eb8ed3cc404fe741d05dbf45847225b8637ef5", "created_at": "2026-11-01T19:00:50Z", "updated_at": "2026-11-01T22:50:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of ATP1B1, a key copy number driver gene in diffuse large B-cell lymphoma and potential target for drugs.", "doi": "10.21037/atm-22-4709", "pmid": "36388804", "authors": ["Shuo Zhang", "Hongmin Wang", "Aichun Liu"], "journal": "Annals of translational medicine", "year": 2022, "abstract": "Background: Copy number variations (CNVs) participate in the development and progression of cancer by altering the expression levels of genes. However, it is unclear whether this correlation exists in diffuse large B-cell lymphoma (DLBCL).\nMethods: Differentially expressed genes (DEGs) were identified from the GSE25638 and GSE56315 datasets. Modules that were highly related to DLBCL prognosis were obtained by Weighted Gene Co-expression Network Analysis (WGCNA). We performed an integrated analysis between CNV and differential gene expression in The Cancer Genome Atlas (TCGA) DLBCL. The DEGs were then overlapped with the module genes and expression-copy number variations-related (Exp-CNV-related) genes to obtain the common key genes. Time-dependent receiver operating characteristic (ROC) analysis was utilized to evaluate the accuracy of the key gene in predicting the prognosis of DLBCL. Next, we conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to explore the key gene. The potential molecule drugs of the key gene were identified by Connectivity Map (Cmap) analysis.\nResults: A turquoise module with 160 genes was identified as the signature module. ATP1B1 is overexpressed in DLBCL cell lines, compared to Cluster of Differentiation 19+B (CD19+B) cells. The ROC curve indicated that ATP1B1 could be a biomarker for diagnosing DLBCL, and the forest map suggested that ATP1B1 gene expression levels had a greater impact on the prognosis of patients with DLBCL. The area under curve (AUC) value of the time-dependent ROC curve with values based on the 1-, 3-, and 5-year survivability were 0.576, 0.663, and 0.706, respectively. Pathway analysis demonstrated the relationship between ATP1B1 and focal adhesion, etc. The inhibitory effects of ATP1B1 downregulation on DLBCL cell proliferation, cell migration, invasion, and cell adhesion were also examined. We found out that the higher proliferation ability in ATP1B1-overexpression cells was rescued with roxithromycin.\nConclusions: ATP1B1 is a copy number driver gene that could potentially be adopted as a diagnostic biomarker and therapeutic target of DLBCL.", "claims": [{"id": "claim-method", "statement": "The R language package DESeq was used to determine DEGs between the DLBCL samples and non-cancerous tissues (adjusted P<10−5 and |log foldchange| >1 as the cut-off criterion), respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36388804", "locator": "sections[3] \"Data collection and identification of DEGs\" paragraph 2", "quote": "The R language package DESeq was used to determine DEGs between the DLBCL samples and non-cancerous tissues (adjusted P<10−5 and |log foldchange| >1 as the cut-off criterion), respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "As for the GSE25638 dataset, 84 DLBCL tissues and 13 normal control tissues were profiled.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36388804", "locator": "sections[3] \"Data collection and identification of DEGs\" paragraph 2", "quote": "As for the GSE25638 dataset, 84 DLBCL tissues and 13 normal control tissues were profiled."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Integrated analysis of GEO expression profiles and TCGA copy-number/expression data identified ATP1B1 as a copy-number-driven key gene in DLBCL, with copy-number amplification in 33.33% of the analyzed TCGA patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36388804", "locator": "sections[18] \"Identification of DLBCL key genes after data integration\" paragraph 2", "quote": "Thereafter, we found that both ATP1B1 and LIMA1 were copy number driven genes, where the copy number amplification of ATP1B1 was 33.33% (48 total patients, 16 patients with increased CNV, Figure 3C), while the copy number amplification of LIMA1 was 20.83% (48 total patients, 10 patients with increased CNV, Figure 3D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Integrated analysis of GEO expression profiles and TCGA copy-number/expression data identified ATP1B1 as a copy-number-driven key gene in DLBCL, with copy-number amplification in 33.33% of the analyzed TCGA patients.", "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:36388804"], "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:GSE10846"], "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:GSE10846"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36388804", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-22-4709", "sha256": 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36388804", "data:geo:GSE10846"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE10846"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:15:51Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 13418, "completion_tokens": 1913, "cached_tokens": 256}}, "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:36388804", "type": "paper", "label": "pmid:36388804"}, {"id": "source:pmid:36388804", "type": "manuscript", "label": "PMID 36388804 full text"}, {"id": "data:geo:GSE10846", "type": "dataset", "label": "GEO GSE10846"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36388804", "type": "paper", "label": "pmid:36388804"}, {"id": "source:pmid:36388804", "type": "manuscript", "label": "PMID 36388804 full text"}, {"id": "data:geo:GSE10846", "type": "dataset", "label": "GEO GSE10846"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36388804", "type": "extraction", "used": ["source:pmid:36388804"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE10846", "type": "accession_resolution", "used": ["data:geo:GSE10846"], "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:36388804", "parent_hash": "sha256:e97c73e868cc29f2c82ebec5939a2d8745e7eb4c9a4bb111fabbf8922eaed4ec", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE10846 licence not read", "asset:data:geo:GSE10846 not downloaded", "asset:data:geo:GSE25638 licence not read", "asset:data:geo:GSE25638 not downloaded", "asset:data:geo:GSE56315 licence not read", "asset:data:geo:GSE56315 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": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Methods Cell culture and transfection Cells from the normal control [Cluster of Di", "ractical guidelines, the Lipofectamine® 2000 transfection reagent (Thermo Fisher, USA Cat. #11668019)", "sher, USA Cat. #11668019) was used for siRNA transfection. After 24 hours, we performed in vitro exper", "ruz Biotechnology, USA Cat.#sc-29,065) after transfection to acquire a stable and consistent cell line"], "order_basis": "paper_text_order:2264", "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 R language package DESeq was used to determine DEGs between the DLBCL samples and non-cancerous tissues (adjusted P<10−5 and |log foldchange| >1 as the cut-off criterion), respectively."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}