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pmid:34497684

Prognostic Nomogram Based on Circular RNA-Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma.

Yang Li · Rongrong Sun · Rui Li · Yonggang Chen · He Du

Oxidative medicine and cellular longevity · 2021 doi:10.1155/2021/9978206

Paper

complete

Experiment

complete

Data

partial

Analysis

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title
Prognostic Nomogram Based on Circular RNA-Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma.
doi
10.1155/2021/9978206
pmid
34497684
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[0]
Yang Li
[1]
Rongrong Sun
[2]
Rui Li
[3]
Yonggang Chen
[4]
He Du
journal
Oxidative medicine and cellular longevity
year
2021
abstract
Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we constructed a circRNA-associated competitive endogenous RNA (ceRNA) network to investigate the regulatory mechanism of LUAD procession and further constructed a prognostic signature to predict overall survival for LUAD patients. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network. Based on the TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs, and 49 DEmRNAs. GO and KEGG enrichment indicated that the ceRNA network might be involved in the regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate Cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using the LASSO method in the TCGA-LUAD training cohort. By applying the signature, patients could be categorized into the high-risk or low-risk subgroups with significant survival differences (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent GEO cohort (GSE42127, HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Multivariate Cox regression analysis proved that the three-gene signature was an independent prognostic factor. Combining the three-gene signature with clinical characters, a nomogram was constructed. The primary and external verification C-indexes were 0.717 and 0.716, respectively. The calibration curves for the probability of 3- and 5-year OS showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and further constructed a useful prognostic signature to guide personalized treatment of LUAD patients.
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Genes with significant association were selected to construct the prognostic signature by the LASSO method using the R package “glmnet” in the TCGA-LUAD training cohort.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34497684", "kind": "science-record", "revision": 7, "content_hash": "sha256:bf695fe6c7827a828050fcc3c7e6aa7ec22736ca958f001beb478af31891ee3e", "created_at": "2026-11-01T15:41:51Z", "updated_at": "2026-11-01T22:04:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic Nomogram Based on Circular RNA-Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma.", "doi": "10.1155/2021/9978206", "pmid": "34497684", "authors": ["Yang Li", "Rongrong Sun", "Rui Li", "Yonggang Chen", "He Du"], "journal": "Oxidative medicine and cellular longevity", "year": 2021, "abstract": "Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we constructed a circRNA-associated competitive endogenous RNA (ceRNA) network to investigate the regulatory mechanism of LUAD procession and further constructed a prognostic signature to predict overall survival for LUAD patients. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network. Based on the TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs, and 49 DEmRNAs. GO and KEGG enrichment indicated that the ceRNA network might be involved in the regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate Cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using the LASSO method in the TCGA-LUAD training cohort. By applying the signature, patients could be categorized into the high-risk or low-risk subgroups with significant survival differences (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009). The prognostic performance was confirmed in an independent GEO cohort (GSE42127, HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004). Multivariate Cox regression analysis proved that the three-gene signature was an independent prognostic factor. Combining the three-gene signature with clinical characters, a nomogram was constructed. The primary and external verification C-indexes were 0.717 and 0.716, respectively. The calibration curves for the probability of 3- and 5-year OS showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and further constructed a useful prognostic signature to guide personalized treatment of LUAD patients.", "claims": [{"id": "claim-method", "statement": "Genes with significant association were selected to construct the prognostic signature by the LASSO method using the R package “glmnet” in the TCGA-LUAD training cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34497684", "locator": "sections[8] \"2.6. Establishment of Prognostic Signature\" paragraph 2", "quote": "Genes with significant association were selected to construct the prognostic signature by the LASSO method using the R package “glmnet” in the TCGA-LUAD training cohort."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The source data of this study were derived from the public repositories, as indicated in Materials and Methods. 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