MAMDC2-AS1 Induces Cuproptosis in Relapsed and Refractory Multiple Myeloma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40344606", "kind": "science-record", "revision": 3, "content_hash": "sha256:0ad895fab3c9761706c5bc126fc926c0d6e09dbd19f0528079869f7d213e9c33", "created_at": "2026-11-01T20:30:30Z", "updated_at": "2026-11-01T22:14:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "MAMDC2-AS1 Induces Cuproptosis in Relapsed and Refractory Multiple Myeloma.", "doi": "10.1002/cnr2.70216", "pmid": "40344606", "authors": ["Yifei Chen", "Jun Liu", "Ying Zhu"], "journal": "Cancer reports (Hoboken, N.J.)", "year": 2025, "abstract": "BACKGROUND: Multiple myeloma is a malignant disorder involving the uncontrolled proliferation of plasma cells in the bone marrow. Prognosis remains poor for individuals with relapsed and refractory multiple myeloma (RRMM), and the underlying mechanisms are yet to be fully understood.\nMETHODS: We collected bone marrow RNA-Seq data from a total of 557 patients with MM from the GEO database (GSE24080) for further analysis, dividing them into relapsed/refractory and control groups. Additionally, we collected bone marrow samples from 57 MM patients to validate the performed RNA-Seq data analysis.\nRESULTS: RNA-Seq analysis of patients with RRMM revealed a significant upregulation of genes associated with cuproptosis. Using the LASSO Cox regression method, several long noncoding RNAs (lncRNAs) were identified that influence copper-induced cell death. Based on these lncRNAs, patients were stratified into high-risk and low-risk groups. The high-risk group exhibited a significantly worse overall survival (OS) compared to the low-risk group, with a p-value of less than 0.001. Our statistical analysis, incorporating LASSO Cox regression, indicated that among these lncRNAs, MAMDC2-AS1 was particularly noteworthy due to its strong correlation with OS (p-value < 0.01). Further validation using qPCR and survival analysis established MAMDC2-AS1 as a strong predictor of prognosis in MM. This finding suggests that MAMDC2-AS1 can serve as a potential independent biomarker for RRMM. The qPCR data validated the RNA-Seq findings and uncovered the significance of MAMDC2-AS1 in the prognosis of this disease.\nCONCLUSION: MAMDC2-AS1 plays a significant role in RRMM. Promisingly, Bortezomib, Bosutinib, Crizotinib, and DMOG have demonstrated promising efficacy in addressing advanced cases.", "claims": [{"id": "claim-method", "statement": "To minimize overfitting, we utilized the “glmnet” package to perform LASSO‐penalized Cox regression, identifying the optimal penalty (λ) through 10‐fold cross‐validation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40344606", "locator": "sections[9] \"Cox Model Construction\" paragraph 2", "quote": "To minimize overfitting, we utilized the “glmnet” package to perform LASSO‐penalized Cox regression, identifying the optimal penalty (λ) through 10‐fold cross‐validation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40344606", "locator": "sections[28] \"Data Availability Statement\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The high‐risk group exhibited a significantly worse overall survival (OS) compared to the low‐risk group, with a p‐value of less than 0.001.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40344606", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The high‐risk group exhibited a significantly worse overall survival (OS) compared to the low‐risk group, with a p‐value of less than 0.001."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The high‐risk group exhibited a significantly worse overall survival (OS) compared to the low‐risk group, with a p‐value of less than 0.001.", "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:40344606"], "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:GSE24080"], "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:GSE24080"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40344606", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/cnr2.70216", "sha256": 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METHODS: We collected bone marrow RNA-Seq data from a total of 557 patients with MM fr", "rom 57 MM patients to validate the performed RNA-Seq data analysis. RESULTS: RNA-Seq analysis of", "he performed RNA-Seq data analysis. RESULTS: RNA-Seq analysis of patients with RRMM revealed a si", "marker for RRMM. The qPCR data validated the RNA-Seq findings and uncovered the significance of M"], "order_basis": "paper_text_order:350", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["S (p-value < 0.01). Further validation using qPCR and survival analysis established MAMDC2-AS1", "otential independent biomarker for RRMM. The qPCR data validated the RNA-Seq findings and unco", "s at our center. After extracting total RNA, qPCR was used to measure the expression changes o"], "order_basis": "paper_text_order:1331", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To minimize overfitting, we utilized the “glmnet” package to perform LASSO‐penalized Cox regression, identifying the optimal penalty (λ) through 10‐fold cross‐validation."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}