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pmid:29069744
Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma.
Jian Xiao · Xiaoxiao Lu · Xi Chen · Yong Zou · Aibin Liu · Wei Li · Bixiu He · Shuya He · Qiong Chen
Oncotarget · 2017 doi:10.18632/oncotarget.17606
Paper
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Experiment
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Data
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Execution
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Complete file
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Accurate diagnosis distinguishing between these two lung cancer types has clinical significance. For this study, we analyzed four Gene Expression Omnibus (GEO) datasets (GSE28571, GSE37745, GSE43580, and GSE50081). We then imported the datasets into the Gene-Cloud of Biotechnology Information online platform to identify genes differentially expressed in LADC and LSCC. We identified DSG3 (desmoglein 3), KRT5 (keratin 5), KRT6A (keratin 6A), KRT6B (keratin 6B), NKX2-1 (NK2 homeobox 1), SFTA2 (surfactant associated 2), SFTA3 (surfactant associated 3), and TMC5 (transmembrane channel-like 5) as potential biomarkers for distinguishing between LADC and LSCC. Receiver operating characteristic curve analysis suggested that KRT5 had the highest diagnostic value for discriminating between these two cancer types. Using the PrognoScan online survival analysis tool and the Kaplan-Meier Plotter, we found that high KRT6A or KRT6B levels, or low NKX2-1, SFTA3, or TMC5 levels correlated with unfavorable prognoses in LADC patients. Further studies will be needed to verify our findings in additional patient samples, and to elucidate the mechanisms of action of these potential biomarkers in non-small cell lung cancer.", "claims": [{"id": "claim-method", "statement": "Using Kaplan-Meier Plotter, we verified that high KRT6A (Hazard ratio, HR=1.66; 95% confidence intervals, 95% CIs: 1.31–2.11; P=1.90E-05) or KRT6B (HR=1.76; 95% CIs: 1.39–2.22; P=1.90E-06) (Figure 6, Table 7), or low NKX2-1 (HR=0.66; 95% CIs: 0.52–0.84; P=0.00051), SFTA3 (HR=0.55; 95% CIs: 0.43–0.70; P=1.20E-06), or TMC5 (HR=0.51; 95% CIs: 0.41–0.65; P=3.30E-08) (Figure 7, Table 7) levels correlated with unfavorable prognosis in LADC patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29069744", "locator": "sections[7] \"Kaplan-meier plotter verified five LADC prognostic factors\" paragraph 2", "quote": "Using Kaplan-Meier Plotter, we verified that high KRT6A (Hazard ratio, HR=1.66; 95% confidence intervals, 95% CIs: 1.31–2.11; P=1.90E-05) or KRT6B (HR=1.76; 95% CIs: 1.39–2.22; P=1.90E-06) (Figure 6, Table 7), or low NKX2-1 (HR=0.66; 95% CIs: 0.52–0.84; P=0.00051), SFTA3 (HR=0.55; 95% CIs: 0.43–0.70; P=1.20E-06), or TMC5 (HR=0.51; 95% CIs: 0.41–0.65; P=3.30E-08) (Figure 7, Table 7) levels correlated with unfavorable prognosis in LADC patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:29069744"], "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. 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dataset, GSE43580", "rows": [["Probe set ID", "Gene symbol", "Gene description", "Gene feature", "Fold change"], ["209125_at", "KRT6A", "keratin 6A", "downregulation", "−53.2466"], ["235075_at", "DSG3", "desmoglein 3", "downregulation", "−45.44"], ["206165_s_at", "CLCA2", "chloride channel accessory 2", "downregulation", "−38.0985"], ["209863_s_at", "TP63", "tumor protein p63", "downregulation", "−28.6096"], ["213796_at", "SPRR1A", "small proline-rich protein 1A", "downregulation", "−27.828"], ["201820_at", "KRT5", "keratin 5", "downregulation", "−26.5195"], ["206032_at", "DSC3", "desmocollin 3", "downregulation", "−25.687"], ["213680_at", "KRT6B", "keratin 6B", "downregulation", "−25.5837"], ["217272_s_at", "SERPINB13", "serpin peptidase inhibitor, clade B (ovalbumin), member 13", "downregulation", "−22.7939"], ["209351_at", "KRT14", "keratin 14", "downregulation", "−21.4751"], ["216623_x_at", "TOX3", "TOX high mobility group box family member 3", "upregulation", "12.48837"], 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"rows": [["Gene symbol", "LADC", "LSCC"], ["", "Dataset", "Case", "HR (95% CIs)", "P-value", "Dataset", "Case", "HR (95% CIs)", "P-value"], ["NKX2-1", "jacob-00182-CANDF", "82", "0.78 (0.64–0.96)", "0.020132", "GSE17710", "56", "0.71 (0.52-0.97)", "0.029764"], ["", "jacob-00182-HLM", "79", "0.78 (0.63–0.97)", "0.027745", "", "", "", ""], ["", "MICHIGAN-LC", "86", "0.56 (0.36–0.87)", "0.009902", "", "", "", ""], ["", "GSE31210", "204", "0.62 (0.43–0.88)", "0.008218", "", "", "", ""], ["", "jacob-00182-UM", "178", "0.81 (0.68–0.97)", "0.021112", "", "", "", ""], ["SFTA2", "-", "-", "-", ">0.05", "-", "-", "-", "-"], ["SFTA3", "GSE13213", "117", "0.89 (0.79–1.00)", "0.048445", "-", "-", "-", "-"], ["", "GSE31210", "204", "0.62 (0.46–0.85)", "0.003019", "", "", "", ""], ["TMC5", "jacob-00182-HLM", "79", "0.45 (0.24–0.84)", "0.012012", "-", "-", "-", ">0.05"], ["", "GSE31210", "204", "0.30 (0.13–0.68)", "0.004014", "", "", "", ""]], "row_count": 12, "column_count": 9, "numeric_cells": 44, "header_rows": 2, "locator": "section[6]/table-wrap[2]#T6"}}, {"id": "asset:table:pmid:29069744:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:13eb585bcd2c36c50aaadd19eaf278b79a3ccbd5370401a6a9c45ae7a21f8063", "bytes": 801, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#T7", "version": null, "note": "Verification of potential prognostic indicators via Kaplan-Meier Plotter", "structure": {"pmcid": "PMC5641087", "section_index": 7, "section_title": "Kaplan-meier plotter verified five LADC prognostic factors", "row_count": 8, "column_count": 7}, "table": {"label": "Table 7", "caption": "Verification of potential prognostic indicators via Kaplan-Meier Plotter", "rows": [["Gene symbol", "LADC", "LSCC"], ["", "Case", "HR (95% CIs)", "P-value", "Case", "HR (95% CIs)", "P-value"], ["DSG3", "673", "1.09 (0.86-1.39)", "0.48", "271", "0.86 (0.63–1.18)", "0.35"], ["KRT6A", "720", "1.66 (1.31–2.11)", "1.90E-05", "524", "0.99 (0.78–1.25)", "0.92"], ["KRT6B", "720", "1.76 (1.39–2.22)", "1.90E-06", "524", "0.94 (0.75–1.20)", "0.63"], ["NKX2-1", "720", "0.66 (0.52–0.84)", "0.00051", "524", "0.82 (0.65–1.04)", "0.11"], ["SFTA3", "673", "0.55 (0.43–0.70)", "1.20E-06", "271", "0.82 (0.60–1.11)", "0.20"], ["TMC5", "720", "0.51 (0.41–0.65)", "3.30E-08", "524", "1.02 (0.8–1.29)", "0.88"]], "row_count": 8, "column_count": 7, "numeric_cells": 39, "header_rows": 2, "locator": "section[7]/table-wrap[1]#T7"}}], "gaps": ["asset:data:geo:GSE28571 not downloaded", "asset:data:geo:GSE28571 licence not read", "asset:data:geo:GSE37745 not downloaded", "asset:data:geo:GSE37745 licence not read", "asset:data:geo:GSE43580 not downloaded", "asset:data:geo:GSE43580 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Using Kaplan-Meier Plotter, we verified that high KRT6A (Hazard ratio, HR=1.66; 95% confidence intervals, 95% CIs: 1.31–2.11; P=1.90E-05) or KRT6B (HR=1.76; 95% CIs: 1.39–2.22; P=1.90E-06) (Figure 6, Table 7), or low NKX2-1 (HR=0.66; 95% CIs: 0.52–0.84; P=0.00051), SFTA3 (HR=0.55; 95% CIs: 0.43–0.70; P=1.20E-06), or TMC5 (HR=0.51; 95% CIs: 0.41–0.65; P=3.30E-08) (Figure 7, Table 7) levels correlated with unfavorable prognosis in LADC patients."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox regression"}}], "targets": [], "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE28571", "GSE37745", "GSE43580", "and GSE50081"], "resolved_accessions": ["GSE28571", "GSE37745", "GSE43580"], "statements": ["The Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/gds) is a public repository at the National Center for Biotechnology Information for storing high throughput gene expression datasets."], "basis": "The paper names GSE28571, GSE37745, GSE43580 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:29069744", "data:geo:GSE28571", "asset:table:pmid:29069744:1", "asset:table:pmid:29069744:2", "asset:table:pmid:29069744:3", "asset:table:pmid:29069744:4", "asset:table:pmid:29069744:5", "asset:table:pmid:29069744:6", "asset:table:pmid:29069744:7"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE28571"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": null, "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 0, "usage": {}}, "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:29069744", "type": "paper", "label": "pmid:29069744"}, {"id": "source:pmid:29069744", "type": "manuscript", "label": "PMID 29069744 full text"}, {"id": "data:geo:GSE28571", "type": "dataset", "label": "GEO GSE28571"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29069744", "type": "paper", "label": "pmid:29069744"}, {"id": "source:pmid:29069744", "type": "manuscript", "label": "PMID 29069744 full text"}, {"id": "data:geo:GSE28571", "type": "dataset", "label": "GEO GSE28571"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29069744", "type": "extraction", "used": ["source:pmid:29069744"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE28571", "type": "accession_resolution", "used": ["data:geo:GSE28571"], "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:29069744", "parent_hash": "sha256:99e64c546d3370d3b7fbadc7547cf571e2b4d95414cfffc05e7387e7faaf933e", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE28571 licence not read", "asset:data:geo:GSE28571 not downloaded", "asset:data:geo:GSE37745 licence not read", "asset:data:geo:GSE37745 not downloaded", "asset:data:geo:GSE43580 licence not read", "asset:data:geo:GSE43580 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": 0.93, "evidence": ["prognostic factor. Because each lung cancer microarray dataset in PrognoScan contained limited case"], "order_basis": "paper_text_order:2894", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using Kaplan-Meier Plotter, we verified that high KRT6A (Hazard ratio, HR=1.66; 95% confidence intervals, 95% CIs: 1.31–2.11; P=1.90E-05) or KRT6B (HR=1.76; 95% CIs: 1.39–2.22; P=1.90E-06) (Figure 6, Table 7), or low NKX2-1 (HR=0.66; 95% CIs: 0.52–0.84; P=0.00051), SFTA3 (HR=0.55; 95% CIs: 0.43–0.70; P=1.20E-06), or TMC5 (HR=0.51; 95% CIs: 0.41–0.65; P=3.30E-08) (Figure 7, Table 7) levels correlated with unfavorable prognosis in LADC patients."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}