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pmid:37158948
Identification and validation of miR-583 and mir-877-5p as biomarkers in patients with breast cancer: an integrated experimental and bioinformatics research.
Zahra Foruzandeh · Mohammad Reza Alivand · Mehdi Ghiami-Rad · Mohammad Zaefizadeh · Saeid Ghorbian
BMC research notes · 2023 doi:10.1186/s13104-023-06343-w
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Complete file
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The advantages of early cancer diagnosis are apparent, and it is a critical factor in increasing the patient's life and survival. According to mounting evidence, microRNAs (miRNAs) may be crucial regulators of critical biological processes. miRNA dysregulation has been linked to the beginning and progression of various human malignancies, including BC, and can operate as tumor suppressors or oncomiRs. This study aimed to identify novel miRNA biomarkers in BC tissues and non-tumor adjacent tissues of patients with BC. Microarray datasets GSE15852 and GSE42568 for differentially expressed genes (DEGs) and GSE45666, GSE57897, and GSE40525 for differentially expressed miRNAs (DEMs) retrieved from the Gene Expression Omnibus (GEO) database were analyzed using \"R\" software. A protein-protein interaction (PPI) network was created to identify the hub genes. MirNet, miRTarBase, and MirPathDB databases were used to predict DEMs targeted genes. Functional enrichment analysis was used to demonstrate the topmost classifications of molecular pathways. The prognostic capability of selected DEMs was evaluated through a Kaplan-Meier plot. Moreover, the specificity and sensitivity of detected miRNAs to discriminate BC from adjacent controls were assessed by area under the curve (AUC) using the ROC curve analysis. In the last phase of this study, gene expression on 100 BC tissues and 100 healthy adjacent tissues were analyzed and calculated by using the Real-Time PCR method.\nRESULTS: This study declared that miR-583 and miR-877-5p were downregulated in tumor samples in comparison to adjacent non-tumor samples (|logFC|< 0 and P ≤ 0.05). Accordingly, ROC curve analysis demonstrated the biomarker potential of miR-877-5p (AUC = 0.63) and miR-583 (AUC = 0.69). Our results showed that has-miR-583 and has-miR-877-5p could be potential biomarkers in BC.", "claims": [{"id": "claim-method", "statement": "The “R” software and “LIMMA” package were employed to efficiently analyze the chosen datasets utilizing correction, quantile normalization, and log2 conversion.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37158948", "locator": "sections[4] \"Identification of DEMs and DEGs\" paragraph 2", "quote": "The “R” software and “LIMMA” package were employed to efficiently analyze the chosen datasets utilizing correction, quantile normalization, and log2 conversion."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All datasets supporting the conclusions of this article are available in NCBI/bioproject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA116827, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA182286, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA195576, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA248377, and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA174219. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37158948", "locator": "sections[29] \"notes\" paragraph 1", "quote": "All datasets supporting the conclusions of this article are available in NCBI/bioproject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA116827, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA182286, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA195576, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA248377, and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA174219. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "miR-583 and miR-877-5p were downregulated in breast cancer tumor samples relative to adjacent non-tumor samples and showed potential as breast cancer biomarkers.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37158948", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "This study declared that miR-583 and miR-877-5p were downregulated in tumor samples in comparison to adjacent non-tumor samples (|logFC|< 0 and P ≤ 0.05)."}, {"asset": "source:pmid:37158948", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Accordingly, ROC curve analysis demonstrated the biomarker potential of miR-877-5p (AUC = 0.63) and miR-583 (AUC = 0.69)."}, {"asset": "source:pmid:37158948", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Our results showed that has-miR-583 and has-miR-877-5p could be potential biomarkers in BC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "miR-583 and miR-877-5p were downregulated in breast cancer tumor samples relative to adjacent non-tumor samples and showed potential as breast cancer biomarkers.", "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:37158948"], "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:GSE15852"], "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:GSE15852"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37158948", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13104-023-06343-w", "sha256": "sha256:c9ded1bc44e04adfde87d672c454d53467e4c928fdcbcde39f1fb9aedcd732d3", "bytes": 25906, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13104-023-06343-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10169388", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE15852", "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=GSE15852", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE15852", "version": null, "note": "All datasets supporting the conclusions of this article are available in NCBI/bioproject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA116827, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA182286, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA195576, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA248377, and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA174219. 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Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All datasets supporting the conclusions of this article are available in NCBI/bioproject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA116827, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA182286, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA195576, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA248377, and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA174219. 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read", "asset:data:geo:GSE40525 not downloaded", "asset:data:geo:GSE40525 licence not read", "asset:data:geo:GSE42568 not downloaded", "asset:data:geo:GSE42568 licence not read", "asset:data:geo:GSE45666 not downloaded", "asset:data:geo:GSE45666 licence not read", "asset:data:geo:GSE57897 not downloaded", "asset:data:geo:GSE57897 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The “R” software and “LIMMA” package were employed to efficiently analyze the chosen datasets utilizing correction, quantile normalization, and log2 conversion."}}, {"id": "method-2", "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-3", "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-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.7, "band": "medium", "quote": "ROC curve"}}], "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": ["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": ["GSE15852", "GSE42568", "GSE45666", "GSE57897", "GSE40525"], "resolved_accessions": ["GSE15852", "GSE42568", "GSE45666", "GSE57897", "GSE40525"], "statements": ["All datasets supporting the conclusions of this article are available in NCBI/bioproject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA116827, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA182286, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA195576, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA248377, and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA174219. Further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE15852, GSE42568, GSE45666, GSE57897, GSE40525 in National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) 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:37158948", "data:geo:GSE15852"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE15852"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:39:02Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8672, "completion_tokens": 1975, "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:37158948", "type": "paper", "label": "pmid:37158948"}, {"id": "source:pmid:37158948", "type": "manuscript", "label": "PMID 37158948 full text"}, {"id": "data:geo:GSE15852", "type": "dataset", "label": "GEO GSE15852"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37158948", "type": "paper", "label": "pmid:37158948"}, {"id": "source:pmid:37158948", "type": "manuscript", "label": "PMID 37158948 full text"}, {"id": "data:geo:GSE15852", "type": "dataset", "label": "GEO GSE15852"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37158948", "type": "extraction", "used": ["source:pmid:37158948"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE15852", "type": "accession_resolution", "used": ["data:geo:GSE15852"], "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:37158948", "parent_hash": "sha256:4232b90d08d32ea8dcd37725101c2b0c1fe422d60d16b7cb33934ac5b0a7d83b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE15852 licence not read", "asset:data:geo:GSE15852 not downloaded", "asset:data:geo:GSE40525 licence not read", "asset:data:geo:GSE40525 not downloaded", "asset:data:geo:GSE42568 licence not read", "asset:data:geo:GSE42568 not downloaded", "asset:data:geo:GSE45666 licence not read", "asset:data:geo:GSE45666 not downloaded", "asset:data:geo:GSE57897 licence not read", "asset:data:geo:GSE57897 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": 0.99, "evidence": ["-tumor adjacent tissues of patients with BC. Microarray datasets GSE15852 and GSE42568 for different", "on DEGs Each of the target genes analyzed by microarray datasets has their pathways enriched. KEGG p"], "order_basis": "paper_text_order:748", "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": 0.93, "evidence": ["es were analyzed and calculated by using the Real-Time PCR method. RESULTS: This study declared that mi"], "order_basis": "paper_text_order:1684", "id": "assay:2"}, {"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” software and “LIMMA” package were employed to efficiently analyze the chosen datasets utilizing correction, quantile normalization, and log2 conversion."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}