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pmid:28415559
Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa.
Lu Feng · John R Houck · Pawadee Lohavanichbutr · Chu Chen
Oncotarget · 2017 doi:10.18632/oncotarget.16358
Paper
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Experiment
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Data
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Analysis
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Complete file
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To better understand the roles long non-coding RNA (lncRNA) play in OSCC carcinogenesis, we compared the expression levels of 3,054 probe sets for lncRNAs between 167 OSCCs and 45 healthy oral mucosa using an Affymetrix HG U133 plus 2.0 array dataset. We found 658 lncRNA transcripts (790 probe sets) to be significantly differentially expressed using a criteria of FDR < 0.01, with 36 of them (39 probe sets) showing more than a 2-fold change. We further validated the top differentially expressed lncRNAs in three independent datasets from Gene Expression Omnibus (GEO) repository: GSE42743, GSE9844, and GSE6791. Fourteen lncRNAs (15 probe sets) were validated in all three datasets using the criteria FDR < 0.01: LOC441178, C5orf66-AS1, HCG22, FLG-AS1, CCL14/CCL15-CCL14, LOC100506990, TRIP10, PCBP1-AS1, LINC01315, LINC00478, COX10-AS1/LOC100506974, MLLT4-AS1, MIR31HG, and DUXAP10/LINC01296. Three lncRNAs in the validated list which showed the highest fold change (LOC441178, HCG22 and C5orf66-AS1) were verified by quantitative RT-PCR in a subset of 20 OSCCs and 10 control samples. In silico prediction of their functional role has given us directions for further investigation.", "claims": [{"id": "claim-method", "statement": "The statistical analysis of differentially expressed lncRNA (between cases and controls) was performed using linear regression, adjusting for age and sex.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28415559", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "The statistical analysis of differentially expressed lncRNA (between cases and controls) was performed using linear regression, adjusting for age and sex."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data were generated using the Affymetrix Human Genome U133 Plus 2.0 array (Affymetrix, Santa Clara, CA, USA) and were deposited in the Gene Expression Omnibus (GEO) Repository under the general accession number GSE30784. 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"downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:28415559:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b1af4f6dc162b9e2c2b2542b7c8b417286015269949b8c1217c3f81f8bbfe8b9", "bytes": 680, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#T1", "version": null, "note": "Characteristics of four microarray datasets used in this study", "structure": {"pmcid": "PMC5458226", "section_index": 3, "section_title": "Differentially expressed lncRNA genes between cases and controls", "row_count": 8, "column_count": 6}, "table": {"label": "Table 1", "caption": "Characteristics of four microarray datasets used in this study", "rows": [["Characteristics", "FHCRC dataset [34] (n = 212)", "GSE42743 [35] (n = 103)", "GSE9844 [36] (n = 38)", "GSE6791 [37] (n = 49)"], ["Case", "Cancer", "167 (OSCC)", "74 (oral cavity)", "26 (tongue)", "35 (OSCC)"], ["Control", "45 (healthy normal)", "29 (adjacent normal)", "12 (adjacent normal)", "14 (non-cancerous normal)"], ["Gender", "Male", "152", "79", "29", "29"], ["Female", "60", "24", "9", "20"], ["Age", "< 50", "64", "29", "11", "7"], ["50~70", "118", "51", "24", "31"], ["> 70", "30", "23", "3", "11"]], "row_count": 8, "column_count": 6, "numeric_cells": 35, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:28415559:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:39eae5944d93c1830f0ae76f14f7924637b4ba0596d8c59dcec5b33aae2a4ca9", "bytes": 4034, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[2]#T2", "version": null, "note": "Validation of 39 differentially expressed probe sets between OSCC and control in three independent datasets", "structure": {"pmcid": "PMC5458226", "section_index": 3, "section_title": "Differentially expressed lncRNA genes between cases and controls", "row_count": 40, "column_count": 8}, "table": {"label": "Table 2", "caption": "Validation of 39 differentially expressed probe sets between OSCC and control in three independent datasets", "rows": [["Probe sets ID", "Gene Symbol", "Chromosomal Location", "Fold change in FHCRC dataset", "Q-value in FHCRC dataset", "Q-value in GSE42743", "Q-value in GSE9844", "Q-value in GSE6791"], ["1563894_at*", "LOC441178", "chr6q27", "–14.50", "8.83E-49", "1.00E-12", "1.11E-06", "6.09E-13"], ["1561685_a_at*", "LOC441178", "chr6q27", "–14.23", "8.83E-49", "5.22E-13", "1.11E-06", "2.26E-13"], ["1558920_at", "SLC8A1-AS1", "chr2p22.1", "–8.43", "5.85E-45", "6.51E-07", "0.02", "1.83E-03"], ["236444_x_at", "C5orf66-AS1", "chr5q31.1", "–6.60", "1.91E-28", "4.32E-09", "2.29E-03", "9.62E-06"], ["227725_at*", "ST6GALNAC1", "chr17q25.1", "–5.87", "1.44E-15", "1.93E-09", "0.02", "1.18E-04"], ["204919_at*", "PRH1-PRR4/PRR4", "chr12p/chr12p13", "–5.31", "4.18E-06", "5.29E-03", "0.59", "0.03"], ["1560767_at*", "HCG22", "chr6p21.33", "–3.95", "1.91E-28", "5.83E-14", "2.35E-05", "1.50E-05"], ["241014_at", "FLG-AS1", "chr1q21.3", "–3.61", "6.52E-35", "5.22E-13", "6.69E-06", "9.62E-06"], ["244620_at", "SLC8A1-AS1", "chr2p22.1", "–3.29", "1.81E-34", "4.33E-06", "0.04", "2.14E-03"], ["224997_x_at", "H19/MIR675", "chr11p15.5", "–3.23", "6.43E-04", "0.05", "0.10", "0.11"], ["205392_s_at*", "CCL14/CCL15-CCL14", "chr17q11.2/chr17q12", "–2.92", "2.08E-14", "1.29E-08", "7.54E-06", "7.39E-07"], ["227917_at", "LOC100506990", "chr8p23.1", "–2.77", "4.44E-21", "1.93E-09", "1.04E-03", "6.38E-04"], ["242546_at", "DUXAP10/LINC01296", "chr14q11.2", "2.75", "3.56E-09", "1.49E-06", "8.29E-03", "3.18E-04"], ["202734_at*", "TRIP10", "chr19p13.3", "–2.69", "4.82E-33", "3.06E-06", "7.44E-03", "6.29E-06"], ["1557389_at", "SH3PXD2A-AS1", "chr10q24.33", "–2.51", "6.31E-14", "2.99E-03", "0.46", "1.03E-03"], ["1554097_a_at", "MIR31HG", "chr9p21.3", "2.50", "1.92E-09", "1.48E-08", "5.59E-03", "8.48E-03"], ["1562921_at", "EP300-AS1", "chr22q13.2", "–2.44", "3.79E-14", "4.87E-03", "0.04", "3.30E-03"], ["228658_at", "MIAT", "chr22q12.1", "2.37", "9.59E-09", "2.31E-04", "0.59", "0.19"], ["236573_at", "MIR1-2/MIR133A1/MIR133A1HG", "chr18q11.2", "–2.34", "2.46E-08", "5.62E-07", "0.17", "0.12"], ["227969_at", "PCBP1-AS1", "chr2p14", "–2.31", "1.24E-35", "6.61E-08", "5.41E-06", "2.18E-04"], ["208908_s_at*", "CAST", "chr5q15", "–2.26", "2.93E-30", "7.59E-06", "0.02", "1.33E-03"], ["229930_at", "LINC01315", "chr22q13.2", "–2.25", "1.77E-22", "6.81E-09", "2.35E-05", "7.86E-06"], ["239999_at", "LINC00478", "chr21q21.1", "–2.25", "2.34E-11", "1.93E-09", "2.35E-05", "1.96E-06"], ["220918_at", "RUNX1-IT1", "chr21q22.12", "2.23", "4.70E-11", "3.42E-07", "0.10", "0.03"], ["202672_s_at*", "ATF3", "chr1q32.3", "2.23", "9.56E-06", "8.20E-05", "0.31", "0.03"], ["1559361_at", "LOC101927668/MACC1", "chr7p21.1", "–2.21", "1.75E-13", "7.55E-04", "0.23", "0.01"], ["230451_at", "COX10-AS1/LOC100506974", "chr17p12", "–2.20", "2.23E-37", "6.63E-09", "1.11E-06", "5.16E-08"], ["219871_at", "KLF3-AS1", "chr4p14", "–2.20", "7.82E-19", "5.00E-08", "0.06", "0.04"], ["238320_at", "MIR612/NEAT1", "chr11q13.1", "2.15", "2.35E-06", "0.02", "0.29", "0.02"], ["207467_x_at*", "CAST", "chr5q15", "–2.14", "1.22E-30", "3.68E-06", "0.01", "1.33E-03"], ["1557146_a_at", "SSTR5-AS1", "chr16p13.3", "–2.12", "7.86E-07", "0.02", "0.40", "0.19"], ["210409_at*", "MLLT4-AS1", "chr6q27", "–2.12", "1.63E-30", "6.45E-07", "1.92E-04", "2.38E-10"], ["226382_at*", "LOC283070", "chr10p13", "–2.09", "9.82E-14", "8.52E-06", "9.58E-03", "0.03"], ["228370_at", "IPW/LOC101930404/PWARSN/SNORD107/SNORD115-13/SNORD115-26/SNORD115-7/SNORD116-22/SNORD116-28/SNORD116-4", "chr15q11.2", "–2.09", "9.34E-08", "1.55E-06", "0.02", "0.04"], ["232034_at", "LINC00537", "chr9q21.11", "–2.05", "1.33E-11", "0.02", "0.10", "0.10"], ["233565_s_at*", "FKBP1A-SDCBP2/SDCBP2", "chr20p13", "–2.05", "1.23E-09", "4.78E-04", "0.17", "0.06"], ["229635_at", "LINC01094", "chr4q21.21", "2.04", "4.78E-12", "9.33E-05", "0.05", "0.01"], ["228564_at", "LINC01116", "chr2q31.1", "2.03", "3.40E-10", "4.94E-08", "0.10", "0.03"], ["227061_at", "LINC01279", "chr3q13.2", "–2.02", "1.63E-03", "5.34E-06", "2.29E-03", "0.19"]], "row_count": 40, "column_count": 8, "numeric_cells": 299, "header_rows": 1, "locator": "section[3]/table-wrap[2]#T2"}}, {"id": "asset:table:pmid:28415559:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d0f356ca5f8ca36f1bca568071f9611689d4417ef1812125fe37dec643bfd2e6", "bytes": 930, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#T3", "version": null, "note": "Functional clustering of the putative predicted targets of LOC441178", "structure": {"pmcid": "PMC5458226", "section_index": 5, "section_title": "Prediction of putative targets of lncRNA LOC441178 and functional clustering", "row_count": 10, "column_count": 5}, "table": {"label": "Table 3", "caption": "Functional clustering of the putative predicted targets of LOC441178", "rows": [["Annotation Cluster 1Enrichment Score: 4.07393095028667"], ["Category", "Term", "Count", "%", "P Value"], ["GOTERM_MF_DIRECT", "GO:0016887~ATPase activity", "11", "11.22449", "1.91E-08"], ["GOTERM_MF_DIRECT", "GO:0003777~microtubule motor activity", "7", "7.142857", "2.46E-06"], ["GOTERM_CC_DIRECT", "GO:0030286~dynein complex", "5", "5.102041", "3.80E-06"], ["GOTERM_BP_DIRECT", "GO:0007018~microtubule-based movement", "6", "6.122449", "5.59E-05"], ["GOTERM_CC_DIRECT", "GO:0005874~microtubule", "8", "8.163265", "8.78E-04"], ["GOTERM_MF_DIRECT", "GO:0005524~ATP binding", "17", "17.34694", "0.002009"], ["KEGG_PATHWAY", "hsa05016:Huntington's disease", "6", "6.122449", "0.003745"], ["GOTERM_CC_DIRECT", "GO:0005929~cilium", "4", "4.081633", "0.038842"]], "row_count": 10, "column_count": 5, "numeric_cells": 33, "header_rows": 2, "locator": "section[5]/table-wrap[1]#T3"}}], "gaps": ["asset:data:geo:GSE30784 not downloaded", "asset:data:geo:GSE30784 licence not read", "asset:data:geo:GSE42743 not downloaded", "asset:data:geo:GSE42743 licence not read", "asset:data:geo:GSE6791 not downloaded", "asset:data:geo:GSE6791 licence not read", "asset:data:geo:GSE9844 not downloaded", "asset:data:geo:GSE9844 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "regression_modelling", "specific": "ols", "label": "Regression modelling", "dsl_operations": ["ols_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The statistical analysis of differentially expressed lncRNA (between cases and controls) was performed using linear regression, adjusting for age and sex."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "ols_fit", "expected_value": 2.0, "unit": "fold change", "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": []}, "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": ["ols_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ols."}, "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": ["GSE30784", "GSE42743", "GSE9844", "GSE6791"], "resolved_accessions": ["GSE30784", "GSE42743", "GSE9844", "GSE6791"], "statements": ["The microarray data were generated using the Affymetrix Human Genome U133 Plus 2.0 array (Affymetrix, Santa Clara, CA, USA) and were deposited in the Gene Expression Omnibus (GEO) Repository under the general accession number GSE30784. The dataset has 212 samples in total, 167 of them are OSCCs and 45 of them are oral mucosa from healthy controls."], "basis": "The paper names GSE30784, GSE42743, GSE9844, GSE6791 in Gene Expression Omnibus (GEO) Repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["ols_fit"], "assets": ["source:pmid:28415559", "data:geo:GSE30784", "asset:table:pmid:28415559:1", "asset:table:pmid:28415559:2", "asset:table:pmid:28415559:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30784"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:51Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 86134, "completion_tokens": 4605, "cached_tokens": 2104}}, "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:28415559", "type": "paper", "label": "pmid:28415559"}, {"id": "source:pmid:28415559", "type": "manuscript", "label": "PMID 28415559 full text"}, {"id": "data:geo:GSE30784", "type": "dataset", "label": "GEO GSE30784"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:28415559", "type": "paper", "label": "pmid:28415559"}, {"id": "source:pmid:28415559", "type": "manuscript", "label": "PMID 28415559 full text"}, {"id": "data:geo:GSE30784", "type": "dataset", "label": "GEO GSE30784"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-28415559", "type": "extraction", "used": ["source:pmid:28415559"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30784", "type": "accession_resolution", "used": ["data:geo:GSE30784"], "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:28415559", "parent_hash": "sha256:79a12f130a0172c46f1e041b477bc9d6a948cb54379bfcaffdc74438f9a13112", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE30784 licence not read", "asset:data:geo:GSE30784 not downloaded", "asset:data:geo:GSE42743 licence not read", "asset:data:geo:GSE42743 not downloaded", "asset:data:geo:GSE6791 licence not read", "asset:data:geo:GSE6791 not downloaded", "asset:data:geo:GSE9844 licence not read", "asset:data:geo:GSE9844 not downloaded", "execution.not_run", "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": 0.77, "evidence": ["67 OSCCs and 45 healthy oral mucosa using an Affymetrix HG U133 plus 2.0 array dataset. We found 658"], "order_basis": "paper_text_order:403", "id": "assay:1"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["ols_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The statistical analysis of differentially expressed lncRNA (between cases and controls) was performed using linear regression, adjusting for age and sex."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}