Integrated Meta-Analysis Identifies Keratin Family Genes and Associated Genes as Key Biomarkers and Therapeutic Targets in Metastatic Cutaneous Melanoma.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40722520", "kind": "science-record", "revision": 2, "content_hash": "sha256:61b1b645930befa37ab07f9279c72a88e4154251b998bb8d67a619a68e45522e", "created_at": "2026-11-01T10:25:52Z", "updated_at": "2026-11-01T14:01:45Z", "generator": {"name": "corpus-assay-engine", "converter": "sep_to_sci_v1", "source_package_schema": "urn:bntrg:sep:1.0.0"}, "paper": {"state": "partial", "title": "Integrated Meta-Analysis Identifies Keratin Family Genes and Associated Genes as Key Biomarkers and Therapeutic Targets in Metastatic Cutaneous Melanoma.", "doi": "10.3390/diagnostics15141770", "pmid": "40722520", "authors": null, "journal": "Diagnostics (Basel, Switzerland)", "year": 2025, "abstract": null, "claims": [{"id": "claim-1", "statement": "the headline numerical result the paper states for its main finding", "kind": "quantitative", "state": "complete", "target": {"value": 11.0, "unit": "hub genes", "tolerance": null, "source": "chars 11258-11503 of source sha256 dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76"}, "evidence": [{"asset": "source:pmid:40722520", "locator": "chars 11258-11503 of source sha256 dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76", "quote": "In this study, through extensive bioinformatics and meta-analysis, we identified 80 DEGs associated with the transition from primary melanoma to metastatic cutaneous melanoma, revealing 11 potential melanoma-associated hub genes—mostly keratins."}]}], "gaps": ["abstract", "authors"]}, "experiment": {"state": "partial", "objective": "the headline numerical result the paper states for its main finding", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate and its interval from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The number a replication must land on, and the sentence it came from.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40722520"], "outputs": ["the published estimate, its unit and its interval"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data behind the published result", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:not_downloaded", "description": "The published result cannot be recomputed without the data the paper analysed.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the analysis programme", "kind": "analysis", "state": "blocked", "blocked_on": "no owned computational capability is bound to this experiment", "description": "Re-run the paper's analysis on the source data and produce the registered result. | SEP input not carried into the asset list: materials:the source data behind the published result in pmid:40722520", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the registered result"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:not_downloaded", "step:run_analysis blocked on no owned computational capability is bound to this experiment", "step:run_analysis input 'materials:the source data behind the published result in pmid:40722520' does not resolve to a declared asset"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40722520", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/diagnostics15141770", "sha256": "sha256:dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76", "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/diagnostics15141770", "version": null, "note": "Source read by the package builder: full_text.", "structure": {"access_state": "full_text"}}, {"id": "asset:table:pmid:40722520:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:80145a203e3d792db1e898dfb2c6ebc63b7a4a09dc9ebdbb12788a11e4704b5e", "bytes": 624, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#diagnostics-15-01770-t001", "version": null, "note": "Core attributes of the four datasets considered in the integrated metastatic melanoma meta-analysis.", "structure": {"pmcid": "PMC12293645", "section_index": 3, "section_title": "2.1. Data Selection and Preprocessing (Inclusion-Exclusion Criteria)", "row_count": 6, "column_count": 4}, "table": {"label": "Table 1", "caption": "Core attributes of the four datasets considered in the integrated metastatic melanoma meta-analysis.", "rows": [["", "", "Melanoma"], ["GEO Name", "Platform", "Primary", "Metastatic"], ["GSE7553 [23]", "GPL570 (Affymetrix Human Genome U133 Plus 2.0)", "46", "12"], ["GSE15605 [24]", "GPL570 (Affymetrix Human Genome U133 Plus 2.0)", "31", "52"], ["GSE46517 [25]", "GPL96 (Affymetrix Human Genome U133A)", "31", "73"], ["GSE8401 [26]", "GPL96 (Affymetrix Human Genome U133A)", "14", "40"]], "row_count": 6, "column_count": 4, "numeric_cells": 16, "header_rows": 1, "locator": "section[3]/table-wrap[1]#diagnostics-15-01770-t001"}}, {"id": "asset:table:pmid:40722520:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6be9104163ad77e8612181469996a52f261c1a5f1661f99dec38df8d0571e082", "bytes": 1077, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#diagnostics-15-01770-t002", "version": null, "note": "Summary of drug–gene interactions retrieved from DGIdb database for the identified hub genes in melanoma metastasis.", "structure": {"pmcid": "PMC12293645", "section_index": 19, "section_title": "3.7. Drug-Gene Network Analysis", "row_count": 11, "column_count": 5}, "table": {"label": "Table 2", "caption": "Summary of drug–gene interactions retrieved from DGIdb database for the identified hub genes in melanoma metastasis.", "rows": [["Gene", "Drug", "Approval Status", "Indication", "Interaction Score"], ["PI3", "PROGESTERONE", "Approved", "Pre-term birth risk reduction", "1.77"], ["KRT10", "EPIDERMAL GROWTH FACTOR", "Not Approved", "Not available", "11.60"], ["DSP", "COMPOUND 66 [PMID: 19788238]", "Not Approved", "Not available", "1.58"], ["DSP", "ENALAPRIL MALEATE", "Approved", "Antihypertensive agent", "1.83"], ["DSP", "NINTEDANIB ESYLATE", "Approved", "Antineoplastic agent", "1.39"], ["CDH1", "FOSBRETABULIN TROMETHAMINE", "Not Approved", "Not available", "13.05"], ["CDH1", "ANTISERUM", "Not Approved", "Not available", "0.75"], ["CDH1", "BICALUTAMIDE", "Approved", "Antineoplastic agent", "1.31"], ["CDH1", "PANCREATIC PROTEOLYTIC ENZYMES", "Not Approved", "Not available", "6.53"], ["FLG", "PROPIONIBACTERIUM ACNES", "Not Approved", "Not available", "52.20"]], "row_count": 11, "column_count": 5, "numeric_cells": 12, "header_rows": 1, "locator": "section[19]/table-wrap[1]#diagnostics-15-01770-t002"}}, {"id": "asset:table:pmid:40722520:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:16e6951e1f1b42a887882817fcec7e6593df7114fa2299e9cf08ad9d50a76c2e", "bytes": 790, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[2]#diagnostics-15-01770-t003", "version": null, "note": "Structural druggability evaluation of hub genes using the AlphaFold-predicted structures and ProteinPlus (DoGSiteScorer). A druggability score above 0.6 indicates high-confidence targets for structure-based drug design.", "structure": {"pmcid": "PMC12293645", "section_index": 19, "section_title": "3.7. Drug-Gene Network Analysis", "row_count": 12, "column_count": 4}, "table": {"label": "Table 3", "caption": "Structural druggability evaluation of hub genes using the AlphaFold-predicted structures and ProteinPlus (DoGSiteScorer). A druggability score above 0.6 indicates high-confidence targets for structure-based drug design.", "rows": [["Pockets", "Gene", "Druggability_Score", "Volume"], ["P 0", "CDH1", "0.80", "1903.56"], ["P 0", "DSP", "0.82", "792.39"], ["P 0", "FLG", "0.80", "3880.47"], ["P 0", "PI3", "0.84", "760.04"], ["P 0", "S100A7", "0.76", "615.68"], ["P 0", "SPRR1B", "0.26", "109.65"], ["P 0", "KRT5", "0.58", "113.20"], ["P 0", "KRT6A", "0.71", "374.28"], ["P 0", "KRT6B", "0.78", "1058.92"], ["P 0", "KRT10", "0.60", "396.39"], ["P 0", "KRT16", "0.80", "1059.57"]], "row_count": 12, "column_count": 4, "numeric_cells": 36, "header_rows": 1, "locator": "section[19]/table-wrap[2]#diagnostics-15-01770-t003"}}], "gaps": ["asset:source:pmid:40722520 not verified"]}, "analysis": {"state": "absent", "methods": [], "targets": [], "gaps": ["method", "targets"]}, "capability": {"state": "absent", "requirements": [], "gaps": ["capability"]}, "readiness": {"state": "partial", "tier": null, "blocking_axis": null, "blocked_on": null, "axes": {}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:40722520", "asset:table:pmid:40722520:1", "asset:table:pmid:40722520:2", "asset:table:pmid:40722520:3"], "steps": ["read_published_estimate"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": ["xml"], "capabilities": [], "data_gaps": ["source:pmid:40722520"]}, "gaps": ["corpus_record_absent"]}, "review": {"state": "partial", "machine_critique": {"status": "blocked", "providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "full-text-reading-v1", "prompt_hash": "df6b3e3ae9cdd5f9822f3dad278730a009ccf12802644eb5bdedf626484786e6", "source_hash": "dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76", "raw_response_sha256": "sha256:e6961ad2fb560514b8104dc966617b689d68ef57b2f481cc6627d917076e16f1", "raw_response_chars": 6560}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "full-text-reading-v1", "prompt_hash": "6cedba3ca86f49a3f90c6036ae1eb0b8a96dd7773f30df9302c6bb6d4b116573", "source_hash": "dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76", "raw_response_sha256": "sha256:215347f38b78b9935e7719866062d0339b0fad547188e82b13a3fab97892a941", "raw_response_chars": 78514}], "target_providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "replication-target-v2", "prompt_hash": "326482fd7976894edeef5c48ceabcb9644218f4fe3bd770aca8cfc208c4b97d9", "source_hash": "dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76", "raw_response": "{\"parent_value\":11,\"unit\":\"hub genes\",\"evidence\":\"In this study, through extensive bioinformatics and meta-analysis, we identified 80 DEGs associated with the transition from primary melanoma to metastatic cutaneous melanoma, revealing 11 potential melanoma-associated hub genes—mostly keratins.\",\"target_result\":\"The paper identifies 11 potential melanoma-associated hub genes, mostly keratins.\",\"number_stated\":true}", "reading": {"parent_value": 11, "unit": "hub genes", "evidence": "In this study, through extensive bioinformatics and meta-analysis, we identified 80 DEGs associated with the transition from primary melanoma to metastatic cutaneous melanoma, revealing 11 potential melanoma-associated hub genes—mostly keratins.", "target_result": "The paper identifies 11 potential melanoma-associated hub genes, mostly keratins.", "number_stated": true, "source_locator": "chars 11258-11503 of source sha256 dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76"}, "recorded_at": "2026-10-31T15:23:33.960755+00:00"}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "replication-target-v2", "prompt_hash": "cfdad3c5debcb74a9384621708b8daf2bff87ea00d5cea573e0ea774dea63972", "source_hash": "dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76", "raw_response": "<think>We need answer JSON only. Need determine headline numerical result main finding. Registered target vague: \"the headline numerical result the paper states for its main finding.\" Need identify likely 11 hub genes? Main finding perhaps \"eleven hub genes\" / conclusion \"80 DEGs ... revealing 11 potential melanoma-associated hub genes—mostly keratins.\" User says single numerical result replication target reproduce, headline number only, value paper itself states for registered target, unit printed. Evidence exact contiguous quote containing number, attribution may attached target. Need parse likely expected parent_value=11, unit maybe \"hub genes\". Evidence quote exact clause from conclusions linking main finding and number: \"In this study, through extensive bioinformatics and meta-analysis, we identified 80 DEGs associated with the transition from primary melanoma to metastatic cutaneous melanoma, revealing 11 potential melanoma-associated hub genes—mostly keratins.\" Could quote whole clause because multiple numbers 80 and 11, attribution. Or abstract Results: \"We identified a total of eleven hub genes associated with melanoma progression.\" Number is word \"eleven\", but parent_value number, unit paper prints. Yet request numerical result, evidence contains number perhaps eleven spelled word. \"Report headline number only: value paper itself states... unit must be unit paper prints.\" Unit could be \"hub genes\". But parent_value schema number. Evidence exact quote contains the number. \"eleven\" counts as number perhaps. Headline likely 11 hub genes. Could quote abstract exact. But \"number\" perhaps numeric notation 11 in conclusion. Better evidence exact contiguous quote: \"In this study, through extensive bioinformatics and meta-analysis, we identified 80 DEGs associated with the transition from primary melanoma to metastatic cutaneous melanoma, revealing 11 potential melanoma-associated hub genes—mostly keratins.\" This has another number 80, but asks single numerical result and whole clause attribution. Could instead quote \"revealing 11 potential melanoma-associated hub genes—mostly keratins.\" Is that a clause and exact contiguous. It directly names target. They say headline number only likely parent_value 11, unit \"hub genes\". target_result maybe \"11 hub genes associated with melanoma progression\" or concise. Need perhaps unit string \"hub genes\". They want headline number only perhaps evidence etc.\n\nCould there be another headline result: 17/33 gene ratio for most enriched pathway? Main finding identified keratin family genes and associated genes biomarkers. Headline numerical result likely 11 hub genes. The prompt often target classification perhaps asks \"headline numerical result the paper states for its main finding\" designed ambiguous. Need extract main headline. Abstract says identified total of eleven hub genes associated progression. Conclusion reinforces 80 DEGs, 11 hub genes. Which is headline numerical result? The title/main finding is genes; number 11. \"headline numerical result\" likely \"11 hub genes.\" Need ensure unit printed exactly? Paper prints \"hub genes\" as unit. Maybe unit should be \"hub genes\" and parent_value 11. Evidence exact quote with numeral 11: conclusion exact sentence. target_result likely \"11 potential melanoma-associated hub genes\". Could state \"11 potential melanoma-associated hub genes—mostly keratins\". Number stated true.\n\nNeed only JSON. Ensure Unicode em dash okay. Evidence exact quote. Is quote whole clause? \"revealing 11 potential melanoma-associated hub genes—mostly keratins.\" exact contiguous yes. Does attribution clearly target? Yes. Could include \"In this study...\" but contains 80 competing headline. Better direct clause from conclusion. Unit paper prints? \"potential melanoma-associated hub genes\" perhaps unit. Usually unit is \"hub genes\". Prompt says unit must be unit paper prints. We should use \"hub genes\" exactly printed. parent_value 11.\n\nLet's formulate valid JSON.</think>\n\n{\"parent_value\":11,\"unit\":\"hub genes\",\"evidence\":\"revealing 11 potential melanoma-associated hub genes—mostly keratins.\",\"target_result\":\"11 potential melanoma-associated hub genes, mostly keratins\",\"number_stated\":true}", "reading": {"parent_value": 11, "unit": "hub genes", "evidence": "revealing 11 potential melanoma-associated hub genes—mostly keratins.", "target_result": "11 potential melanoma-associated hub genes, mostly keratins", "number_stated": true, "source_locator": "chars 11434-11503 of source sha256 dbe0cba1ae6a1453bdf78565aa1317752979d1d38c9b70efa05d9491e21dff76"}, "recorded_at": "2026-10-31T15:23:50.966796+00:00"}], "agreement": false, "disagreements": {"target_result": {"minimax": "The main finding was 80 metastasis-associated differentially expressed genes, with 11 potential melanoma-associated hub genes, mostly keratins.", "minimax_alt": "A total of eleven hub genes associated with melanoma progression, mostly members of the keratin gene family.", "decisive": false}, "analysis_methods": {"minimax": ["Integrated meta-analysis", "limma", "edgeR", "ComBat batch-effect correction", "RobustRankAggreg (RRA)", "DExMA", "Fisher’s method", "EPIC immune-cell deconvolution", "Spearman correlation", "GO/KEGG functional enrichment analysis", "Benjamini-Hochberg false discovery rate", "Protein-protein interaction network analysis", "Topological hub-gene identification using Betweenness, MCC, Degree, and Bottleneck", "TCGA-SKCM validation", "DGIdb drug-gene interaction analysis", "ProteinPlus and AlphaFold structural druggability analysis"], "minimax_alt": ["Quantile normalization and filtering of lowly expressed genes", "limma differential-expression analysis", "edgeR differential-expression analysis", "ComBat batch-effect correction", "RobustRankAggreg (RRA) using aggregateRanks", "DExMA metaAnalysisDE", "Fisher’s method for integrated meta-analysis", "Protein-protein interaction network construction", "Betweenness, MCC, Degree, and Bottleneck topological methods for hub-gene identification", "EPIC immune-cell deconvolution via immunedeconv", "Spearman correlation", "GO and KEGG enrichment analysis via clusterProfiler and enrichplot", "Benjamini-Hochberg false-discovery-rate correction", "TCGA-SKCM cohort validation", "DGIdb drug-gene interaction analysis", "Cytoscape drug-gene network construction", "AlphaFold protein-structure retrieval and ProteinPlus DogSiteScore druggability assessment"], "decisive": false}, "statistical_method": {"minimax": "Fisher’s method", "minimax_alt": "Hub-gene identification using four topological methods: Betweenness, MCC, Degree, and Bottleneck.", "decisive": true}}, "agreement_basis": {"policy": "decisive_fields", "decisive_fields": ["work_type", "number_stated", "parent_value", "unit"]}, "blinded": true}, "human_critique": {"status": "not_run", "reviewer": null, "signed_at": null, "conflict_checked": false, "commentary": null}, "stages": [{"key": "target_materials", "status": "pending", "reason": null, "evidence": null}, {"key": "independent_readings", "status": "blocked", "reason": "The independent readings are incomplete or disagree; the source evidence must resolve the difference.", "evidence": {"provider_errors": []}}, {"key": "source_resolution", "status": "pending", "reason": null, "evidence": null}, {"key": "protocol_reconstruction", "status": "pending", "reason": null, "evidence": null}, {"key": "control_execution", "status": "pending", "reason": null, "evidence": null}, {"key": "control_comparison", "status": "pending", "reason": null, "evidence": null}, {"key": "publication", "status": "pending", "reason": null, "evidence": null}], "gaps": ["review.human_critique", "review.machine_critique.blocked"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "package:19ad7947f7c6056d7fe8e380deed6d6d95d2e8f87141e58200bb13b1da46bcf5", "type": "sep_package", "label": "SEP v1 package for pmid:40722520"}], "activities": [{"id": "activity:conversion:pmid:40722520", "type": "conversion", "used": ["package:19ad7947f7c6056d7fe8e380deed6d6d95d2e8f87141e58200bb13b1da46bcf5"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:minimax", "type": "model", "label": "minimax"}, {"id": "agent:minimax_alt", "type": "model", "label": "minimax_alt"}, {"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}], "source_run_id": "run-20261023T122449232913", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40722520", "parent_hash": "sha256:e7bf378b5f100e12433bd8907778511f40c458c568b9b1de67985496703a6815", "fork_of": null, "generation": 2}, "gaps": ["abstract", "asset:source:pmid:40722520 not verified", "authors", "capability", "corpus_record_absent", "execution.not_run", "method", "review.human_critique", "review.machine_critique.blocked", "step:obtain_source_data blocked on data:not_downloaded", "step:run_analysis blocked on no owned computational capability is bound to this experiment", "step:run_analysis input 'materials:the source data behind the published result in pmid:40722520' does not resolve to a declared asset", "targets"]}