Identification and validation of an eight-lncRNA signature that predicts prognosis in patients with esophageal squamous cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35578166", "kind": "science-record", "revision": 5, "content_hash": "sha256:fec5bc498cb0af65ce83924a14a033c8b1ac60362719afd342e93787bbdac620", "created_at": "2026-11-01T18:14:28Z", "updated_at": "2026-11-01T22:49:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of an eight-lncRNA signature that predicts prognosis in patients with esophageal squamous cell carcinoma.", "doi": "10.1186/s11658-022-00331-x", "pmid": "35578166", "authors": ["Jinfeng Zhang", "Xiaodong Ling", "Chengyuan Fang", "Jianqun Ma"], "journal": "Cellular & molecular biology letters", "year": 2022, "abstract": "BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is correlated with worse clinical prognosis and lacks available targeted therapy. Thus, identification of reliable biomarkers is required for the diagnosis and treatment of ESCC.\nMETHODS: We downloaded the GSE53625 dataset as a training dataset to screen differentially expressed RNAs (DERs) with the criterion of false discovery rate (FDR) < 0.05 and |log2fold change (FC)| > 1. A support vector machine classifier was used to find the optimal feature gene set that could conclusively distinguish different samples. An eight-lncRNA signature was identified by random survival forest algorithm and multivariate Cox regression analysis. The RNA sequencing data from The Cancer Genome Atlas (TCGA) database were used for external validation. The predictive value of the signature was assessed using Kaplan-Meier test, time-dependent receiver operating characteristic (ROC) curves, and dynamic area under the curve (AUC). Furthermore, a nomogram to predict patients' 3-year and 5-year prognosis was constructed. CCK-8 assay, flow cytometry, and transwell assay were conducted in ESCC cells.\nRESULTS: A total of 1136 DERs, including 689 downregulated mRNAs, 318 upregulated mRNAs, 74 downregulated lncRNAs and 55 upregulated lncRNAs, were obtained in the GES53625 dataset. From the training dataset, we identified an eight-lncRNA signature, (ADAMTS9-AS1, DLX6-AS1, LINC00470, LINC00520, LINC01497, LINC01749, MAMDC2-AS1, and SSTR5-AS1). A nomogram based on the eight-lncRNA signature, age, and pathologic stage was developed and showed good accuracy for predicting 3-year and 5-year survival probability of patients with ESCC. Functionally, knockdown of LINC00470 significantly suppressed cell proliferation, G1/S transition, and migration in two ESCC cell lines (EC9706 and TE-9). Moreover, knockdown of LINC00470 downregulated the protein levels of PCNA, CDK4, and N-cadherin, while upregulating E-cadherin protein level in EC9706 and TE-9 cells.\nCONCLUSION: Our eight-lncRNA signature and nomogram can provide theoretical guidance for further research on the molecular mechanism of ESCC and the screening of molecular markers.", "claims": [{"id": "claim-method", "statement": "On the basis of the optimal feature genes, signature lncRNAs correlated with independent prognosis were identified using a multivariable Cox proportional hazards model implemented with the R3.4.1 survival package version 2.41–1 [19] with log-rank p-value < 0.05 as the cutoff criterion.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35578166", "locator": "sections[6] \"Identification of signature lncRNAs and RS calculation\" paragraph 2", "quote": "On the basis of the optimal feature genes, signature lncRNAs correlated with independent prognosis were identified using a multivariable Cox proportional hazards model implemented with the R3.4.1 survival package version 2.41–1 [19] with log-rank p-value < 0.05 as the cutoff criterion."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile GSE53625 [14], including 179 ESCC tumor samples and matched controls, was downloaded from Gene Expression Omnibus (GEO: http://www.ncbi.nlm.nih.gov/geo/) database [15] under the GPL18109 platform (Agilent human lncRNA + mRNA array V.2.0). These 179 samples from GEO were used as a training set.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35578166", "locator": "sections[3] \"Dataset preparation\" paragraph 2", "quote": "The gene expression profile GSE53625 [14], including 179 ESCC tumor samples and matched controls, was downloaded from Gene Expression Omnibus (GEO: http://www.ncbi.nlm.nih.gov/geo/) database [15] under the GPL18109 platform (Agilent human lncRNA + mRNA array V.2.0). These 179 samples from GEO were used as a training set."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Moreover, the age, pathologic stage, and RS model status based on the eight-lncRNA signature remained three independent predictors.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35578166", "locator": "sections[21] \"The eight-lncRNA signature was an independent predictor of ESCC prognosis\" paragraph 2", "quote": "Moreover, the age, pathologic stage, and RS model status based on the eight-lncRNA signature remained three independent predictors."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Moreover, the age, pathologic stage, and RS model status based on the eight-lncRNA signature remained three independent predictors.", "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:35578166"], "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:GSE53625"], "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:GSE53625"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35578166", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s11658-022-00331-x", "sha256": "sha256:d96b2fb0f7c3dd0d194b5ddd8bd6740ac83b485a5cf1707ce833276b80d20346", "bytes": 38357, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s11658-022-00331-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9109328", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE53625", "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=GSE53625", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE53625", "version": null, "note": "The gene expression profile GSE53625 [14], including 179 ESCC tumor samples and matched controls, was downloaded from Gene Expression Omnibus (GEO: http://www.ncbi.nlm.nih.gov/geo/) database [15] under the GPL18109 platform (Agilent human lncRNA + mRNA array V.2.0). 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CCK-8 assay, flow cytometry, and transwell assay were conducted in ESCC"], "order_basis": "paper_text_order:1167", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ability of patients with ESCC. Functionally, knockdown of LINC00470 significantly suppressed cell p", "ESCC cell lines (EC9706 and TE-9). Moreover, knockdown of LINC00470 downregulated the protein level"], "order_basis": "paper_text_order:1782", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["my of Sciences (Shanghai, China), which were cultured in DMEM with 10% FBS (Gibco, USA) at 37 °C cont"], "order_basis": "paper_text_order:3642", "id": "assay:5"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["On the basis of the optimal feature genes, signature lncRNAs correlated with independent prognosis were identified using a multivariable Cox proportional hazards model implemented with the R3.4.1 survival package version 2.41–1 [19] with log-rank p-value < 0.05 as the cutoff criterion."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}