Identification of a circadian gene signature that predicts overall survival in lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34285836", "kind": "science-record", "revision": 6, "content_hash": "sha256:75e51817f5c53fe275de4b18c5e51bd3dea9d89cb540a44d14d90e3333a3f54a", "created_at": "2026-11-01T15:41:44Z", "updated_at": "2026-11-01T21:25:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a circadian gene signature that predicts overall survival in lung adenocarcinoma.", "doi": "10.7717/peerj.11733", "pmid": "34285836", "authors": ["Xinliang Gao", "Mingbo Tang", "Suyan Tian", "Jialin Li", "Wei Liu"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer which is the leading cause of death in cancer patients. Circadian clock disruption has been listed as a likely carcinogen. However, whether the expression of circadian genes affects overall survival (OS) in LUAD patients remains unknown. In this article, we identified a circadian gene signature to predict overall survival in LUAD.\nMETHODS: RNA sequencing (HTSeq-FPKM) data and clinical characteristics were obtained for a cohort of LUAD patients from The Cancer Genome Atlas (TCGA). A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database.\nRESULTS: Five differentially expressed genes (DEGs) were identified to be significantly associated with OS using univariate Cox proportional regression analysis (P < 0.05). Patients classified as high risk based on these five DEGs had significantly lower OS than those classified as low risk in both the TGCA cohort and GSE72094 dataset (P < 0.001). Multivariate Cox regression analysis revealed that the five-gene-signature based risk score was an independent predictor of OS (hazard ratio > 1, P < 0.001). Receiver operating characteristic (ROC) curves confirmed its prognostic value. Gene set enrichment analysis (GSEA) showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cell proliferation, gene damage repair, proteasomes, and immune and autoimmune diseases were significantly enriched.\nCONCLUSION: A novel circadian gene signature for OS in LUAD was found to be predictive in both the derivation and validation cohorts. Targeting circadian genes is a potential therapeutic option in LUAD.", "claims": [{"id": "claim-method", "statement": "A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34285836", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:Data is available at TCGA-LUAD (https://portal.gdc.cancer.gov/repository), and at NCBI GEO: GSE72094.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34285836", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The following information was supplied regarding data availability:Data is available at TCGA-LUAD (https://portal.gdc.cancer.gov/repository), and at NCBI GEO: GSE72094."}], "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:34285836"], "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:GSE72094"], "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:GSE72094"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34285836", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.11733", "sha256": "sha256:65c7773f89ca98c2123a7147ad48bd80f5b78c89eb47248929288aa87b0de093", "bytes": 37081, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.11733", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8272922", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE72094", "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=GSE72094", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE72094", "version": null, "note": "The following information was supplied regarding data availability:Data is available at TCGA-LUAD 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212 (45.2%)", "172 (52.4%) 156 (47.6%)", "P = 0.559"], ["TNM Stage I II III IV", "257 (54.8%) 112 (23.9%) 75 (16.0%) 25 (5.3%)", "218 (66.5%) 53 (16.2%) 46 (14.0%) 11 (3.4%)", "P = 0.007"], ["Smoking history Non-smoker Smoker", "69 (14.7%) 400 (85.3%)", "30 (9.1%) 298 (90.9%)", "P = 0.025"], ["Median OS (days)", "629", "842", "P = 0.034"]], "row_count": 7, "column_count": 4, "numeric_cells": 18, "header_rows": 1, "locator": "section[8]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:34285836:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c0bf8bc175c4dc130d1d4a2dfc67d8b936609c2faa428a45de5bcde322126107", "bytes": 1026, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#table-2", "version": null, "note": "Risk factors affecting OS in the TCGA LUAD cohort and GSE72094.", "structure": {"pmcid": "PMC8272922", "section_index": 12, 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