Identification of Gefitinib Resistance-Related lncRNA-miRNA-mRNA Regulatory Networks and Corresponding Prognostic Signature in Patients with Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36118184", "kind": "science-record", "revision": 4, "content_hash": "sha256:fd7162b242035ef108d38bdf1417e9d05554be783adafa4086af093745f850e7", "created_at": "2026-11-01T18:15:23Z", "updated_at": "2026-11-01T22:07:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Gefitinib Resistance-Related lncRNA-miRNA-mRNA Regulatory Networks and Corresponding Prognostic Signature in Patients with Lung Adenocarcinoma.", "doi": "10.2147/IJGM.S369718", "pmid": "36118184", "authors": ["Taoli Wang", "Zhulin Wu", "Shiguang Li", "Zhong Chen", "Yiqi Chen", "Zhenjiang Yang"], "journal": "International journal of general medicine", "year": 2022, "abstract": "Purpose: To identify and characterize gefitinib resistance-related (GefR-related) lncRNAs and construct a prediction model for lung adenocarcinoma (LUAD).\nMethods: Differential expression analysis between PC9 and gefitinib-resistant PC9 (PC9GR) cell samples was performed to screen GefR-related lncRNAs and mRNAs based on the GSE34228 dataset. These lncRNAs, mRNAs, and their corresponding microRNAs (miRNAs) were used to construct the GefR-related network and PPI networks. Functional enrichment analyses were conducted using the STRING database. A prognostic signature was developed using the TCGA dataset. The reliability of the signature was tested using the Kaplan-Meier method and ROC curve. Lastly, the FZD4-associated ceRNA subnetwork was selected to confirm the in vitro expressions of the GefR-related lncRNAs using RT-qPCR assay.\nResults: A GefR-related ceRNA network that consists of 35 miRNAs, 26 lncRNAs, and 179 mRNAs was constructed. Then, 20 hub genes were screened from the targeted mRNAs of the constructed PPI network, and enrichment analysis identified relevant enriched pathways. We also constructed a prognostic signature for LUAD based on nine mRNAs in the GefR-related ceRNA network. The 9-mRNA signature was an independent predictor of LUAD, the AUC produced by ROC analysis showed a good predictive power of the model, and Kaplan-Meier analysis showed poorer outcomes in the high-risk group, relative to the low-risk group. Lastly, MIR137HG and ZNF295-AS1 levels were found to be associated with gefitinib resistance and exerted their functions through the ceRNA mechanism.\nConclusion: We established a prognostic signature and identified two lncRNAs (MIR137HG and ZNF295-AS1) with potential significant roles in gefitinib resistance.", "claims": [{"id": "claim-method", "statement": "A Cox proportional hazard model was used for univariate and multivariate analyses using the “survival” package in R software, and potential prognosis-related mRNAs in ceRNA network with p < 0.05 in univariate analysis subjected to multivariate Cox regression analysis, which then determined the prognostic value of specific gene signatures.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36118184", "locator": "sections[10] \"Establishment and Verification of GefR-Related mRNAs Prognostic Signature\" paragraph 2", "quote": "A Cox proportional hazard model was used for univariate and multivariate analyses using the “survival” package in R software, and potential prognosis-related mRNAs in ceRNA network with p < 0.05 in univariate analysis subjected to multivariate Cox regression analysis, which then determined the prognostic value of specific gene signatures."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and analyzed during the study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36118184", "locator": "sections[26] \"Data Sharing Statement\" paragraph 2", "quote": "The datasets used and analyzed during the study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The nine-mRNA signature was an independent predictor of LUAD, with an ROC AUC of 0.781, and high-risk patients had poorer outcomes than low-risk patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36118184", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The 9-mRNA signature was an independent predictor of LUAD, the AUC produced by ROC analysis showed a good predictive power of the model, and Kaplan–Meier analysis showed poorer outcomes in the high-risk group, relative to the low-risk group."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The nine-mRNA signature was an independent predictor of LUAD, with an ROC AUC of 0.781, and high-risk patients had poorer outcomes than low-risk patients.", "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:36118184"], "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:GSE34228"], "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:GSE34228"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36118184", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S369718", "sha256": "sha256:b702fe0d71a384109897153be56cf338aeb9b0c2b8acfafc937ba123bcc20a4e", "bytes": 35832, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S369718", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9477152", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE34228", "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=GSE34228", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE34228", "version": null, "note": "The datasets used and analyzed during the study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and analyzed during the study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM844917", "GSM844918", "GSM844919", "GSM844920", "GSM844921", "GSM844922", "GSM844923", "GSM844924", "GSM844925", "GSM844926", "GSM844927", "GSM844928", "GSM844929", "GSM844930", "GSM844931", "GSM844932", "GSM844933", "GSM844934", "GSM844935", "GSM844936", "GSM844937", "GSM844938", "GSM844939", "GSM844940", "GSM844941", "GSM844942", "GSM844943", "GSM844944", "GSM844945", "GSM844946", "GSM844947", "GSM844948", "GSM844949", "GSM844950", "GSM844951", "GSM844952", "GSM844953", "GSM844954", "GSM844955", "GSM844956", "GSM844957", "GSM844958", "GSM844959", "GSM844960", "GSM844961", "GSM844962", "GSM844963", "GSM844964", "GSM844965", "GSM844966", "GSM844967", "GSM844968", "GSM844969", "GSM844970", "GSM844971", "GSM844972", "GSM844973", "GSM844974", "GSM844975", "GSM844976", "GSM844977", "GSM844978", "GSM844979", "GSM844980", "GSM844981", "GSM844982", "GSM844983", "GSM844984", "GSM844985", "GSM844986", "GSM844987", "GSM844988", "GSM844989", "GSM844990", "GSM844991", "GSM844992", "GSM844993", "GSM844994", "GSM844995", "GSM844996", "GSM844997", "GSM844998", "GSM844999", "GSM845000", "GSM845001", "GSM845002", "GSM845003", "GSM845004", "GSM845005", "GSM845006", "GSM845007", "GSM845008", "GSM845009", "GSM845010", "GSM845011", "GSM845012", "GSM845013", "GSM845014", "GSM845015", "GSM845016", "GSM845017", "GSM845018", "GSM845019", "GSM845020", "GSM845021", "GSM845022", "GSM845023", "GSM845024", "GSM845025", "GSM845026", "GSM845027", "GSM845028", "GSM845029", "GSM845030", "GSM845031", "GSM845032", "GSM845033", "GSM845034", "GSM845035", "GSM845036", "GSM845037", "GSM845038", "GSM845039", "GSM845040", "GSM845041", "GSM845042", "GSM845043", "GSM845044", "GSM845045", "GSM845046", "GSM845047", "GSM845048", "GSM845049", "GSM845050", "GSM845051", "GSM845052", "GSM845053", "GSM845054", "GSM845055", "GSM845056", "GSM845057", "GSM845058", "GSM845059", "GSM845060", "GSM845061", "GSM845062", "GSM845063", "GSM845064", "GSM845065", "GSM845066", "GSM845067", "GSM845068", "GSM845069", "GSM845070", "GSM845071", "GSM845072", "GSM845073", "GSM845074", "GSM845075", "GSM845076", "GSM845077", "GSM845078", "GSM845079", "GSM845080", "GSM845081", "GSM845082", "GSM845083", "GSM845084", "GSM845085", "GSM845086", "GSM845087", "GSM845088", "GSM845089", "GSM845090", "GSM845091", "GSM845092", "GSM845093", "GSM845094", "GSM845095", "GSM845096", "GSM845097", "GSM845098", "GSM845099", "GSM845100", "GSM845101", "GSM845102", "GSM845103", "GSM845104", "GSM845105", "GSM845106", "GSM845107", "GSM845108", "GSM845109", "GSM845110", "GSM845111", "GSM845112", "GSM845113", "GSM845114", "GSM845115", "GSM845116", "GSM845117", "GSM845118", "GSM845119", "GSM845120", "GSM845121", "GSM845122", "GSM845123", "GSM845124"], "sample_count": 208, "group_sizes": null, "group_sizes_basis": null, "platform": "4133", "taxon": "Homo sapiens", "title": "Time-course gene expression profiles of gefitinib-sensitive or -resistant lung adenocarcinoma cells stimulated with EGF, in the presence or absence of gefitinib, EGF receptor tyrosine kinase-specific inhibitor", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE34228 not downloaded", "asset:data:geo:GSE34228 licence not read"]}, "analysis": {"state": "partial", "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": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"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"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-4", "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": "PPI"}}, {"id": "method-5", "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"}}, {"id": "method-6", "family": null, "specific": null, "label": "Cox proportional hazard model with univariate and multivariate analyses", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A Cox proportional hazard model was used for univariate and multivariate analyses using the “survival” package in R software, and potential prognosis-related mRNAs in ceRNA network with p < 0.05 in univariate analysis subjected to multivariate Cox regression analysis, which then determined the prognostic value of specific gene signatures."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["GSE34228"], "resolved_accessions": ["GSE34228"], "statements": ["The datasets used and analyzed during the study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE34228 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:36118184", "data:geo:GSE34228"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE34228"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:05:54Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10931, "completion_tokens": 1381, "cached_tokens": 256}}, "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:36118184", "type": "paper", "label": "pmid:36118184"}, {"id": "source:pmid:36118184", "type": "manuscript", "label": "PMID 36118184 full text"}, {"id": "data:geo:GSE34228", "type": "dataset", "label": "GEO GSE34228"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36118184", "type": "paper", "label": "pmid:36118184"}, {"id": "source:pmid:36118184", "type": "manuscript", "label": "PMID 36118184 full text"}, {"id": "data:geo:GSE34228", "type": "dataset", "label": "GEO GSE34228"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36118184", "type": "extraction", "used": ["source:pmid:36118184"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE34228", "type": "accession_resolution", "used": ["data:geo:GSE34228"], "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:36118184", "parent_hash": "sha256:7bf54d12275ae2e41f5d3039cb99350fabc224210b1e79fe7e223a90bb1d15c8", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE34228 licence not read", "asset:data:geo:GSE34228 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["xpressions of the GefR-related lncRNAs using RT-qPCR assay. Results: A GefR-related ceRNA network", "essions of the GefR-related lncRNAs using RT-qPCR assay. Results: A GefR-related ceRNA network"], "order_basis": "paper_text_order:943", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["). To obtain the PC9GR cells, PC9 cells were cultured with a stepwise increase in the concentrations of", "for 6 months. In addition, PC9GR cells were cultured in a medium containing 10 nM of gefitinib to ma"], "order_basis": "paper_text_order:2776", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["r 48 hours, cell viability was monitored via MTT (Beyotime, China) following the manufacturer", "tinib sensitivity of PC9 and PC9GR cells via MTT (\\documentclass[12pt]{minimal} \\usepackage{w"], "order_basis": "paper_text_order:3352", "id": "assay:3"}, {"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": 0.7, "evidence": ["Kaplan-Meier"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}