Prognostic Value and Genome Signature of m6A/m5C Regulated Genes in Early-Stage Lung Adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37047493", "kind": "science-record", "revision": 3, "content_hash": "sha256:e65c7c9050f5343e274bef2e942a8479b45552840f99dbbc82c660b1190a6371", "created_at": "2026-11-01T19:01:42Z", "updated_at": "2026-11-01T22:09:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic Value and Genome Signature of m6A/m5C Regulated Genes in Early-Stage Lung Adenocarcinoma.", "doi": "10.3390/ijms24076520", "pmid": "37047493", "authors": ["Long Tian", "Yan Wang", "Jie Tian", "Wenpeng Song", "Lu Li", "Guowei Che"], "journal": "International journal of molecular sciences", "year": 2023, "abstract": "RNA modifications implicate pathological and prognosis significance in cancer development and progression, of which, m6A and m5C are representative regulators. These RNA modifications could produce effects on the function of other RNA by regulating gene expression. Thus, in this study, we aimed to explore the correlation between m6A/m5C regulators and early-stage lung adenocarcinoma (LUAD). Only the early-stage LUAD samples were included in this investigation, and the RNA-seq dataset of The Cancer Genome Atlas (TCGA) cohort was utilized to evaluate the expression of 37 m6A/m5C regulated genes. Based on the expression level of these 37 genes, early-stage LUAD patients were divided into 2 clusters, which were performed by consensus clustering, and the m6A/m5C subtypes had significantly different prognostic outcomes (p < 0.001). Cluster1, which has a better prognosis, was characterized by the C3 (inflammatory) immune subtype, low immune infiltration, chemokine expression, major histocompatibility complex (MHC) expression, and immune checkpoint molecule expression. Furthermore, compared with cluster1, cluster2 showed a T cell exhaustion state, characterized by a high expression of immune checkpoint genes, and immune cells, such as T cells, CD8+ T cells, cytotoxic lymphocytes, NK cells, and so on. In addition, patients in cluster2 were with high tumor mutational burden (TMB) and numerous significant mutated oncogene and tumor suppressor genes, such as WNT10B, ERBB4, SMARCA4, TP53, and CDKN2A (p < 0.001). A total of 19 genes were mostly related to the prognosis of LUAD and were upregulated in cluster2 (p < 0.05), showing a positive correlation with the mRNA expression of 37 m6A/m5C regulated genes. The predictive risk model was constructed using Cox and LASSO (least absolute shrinkage and selection operator) regression analysis. Finally, a seven-gene m6A/m5C risk model, comprising of METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7, was constructed to stratify the prognosis of early-stage LUAD (p = 0.0049, AUC = 0.791). The high-risk score was associated with a poorer prognosis. This model was also validated using two additional GEO datasets: GSE72094 (p = 0.011, AUC = 0.736) and GSE50081 (p = 0.012, AUC = 0.628). In summary, it was established that the m6A/m5C-regulated genes performed a crosstalk function in the mRNA expression of early-stage LUAD. By interacting with other mRNA genes, m6A/m5C modification disturbs DNA replication and the tumor immune microenvironment (TIME). The seven-gene risk model may be a critical tool for the prognostic assessment of early-stage LUAD.", "claims": [{"id": "claim-method", "statement": "The best prognostic signatures were screened from 37 m6A/m5C-related regulatory genes by LASSO-Cox regression (Figure 6A,B) and multivariate Cox analysis (Figure 6C).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37047493", "locator": "sections[8] \"2.6. Construction of the m6A/m5C Related Prognostic Model\" paragraph 2", "quote": "The best prognostic signatures were screened from 37 m6A/m5C-related regulatory genes by LASSO-Cox regression (Figure 6A,B) and multivariate Cox analysis (Figure 6C)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original cohorts data presented in the study are included in the Supplementary Tables. More information is available upon reasonable request from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37047493", "locator": "sections[25] \"notes\" paragraph 1", "quote": "The original cohorts data presented in the study are included in the Supplementary Tables. More information is available upon reasonable request from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A seven-gene m6A/m5C risk model comprising METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7 stratified early-stage LUAD prognosis with p = 0.0049 and AUC = 0.791, with high risk associated with poorer prognosis.", "kind": "quantitative", "target": {"value": 0.791, "unit": "auc", "tolerance": null, "source": "Finally, a seven-gene m6A/m5C risk model, comprising of METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7, was constructed to stratify the prognosis of early-stage LUAD (p = 0.0049, AUC = 0.791)."}, "evidence": [{"asset": "source:pmid:37047493", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Finally, a seven-gene m6A/m5C risk model, comprising of METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7, was constructed to stratify the prognosis of early-stage LUAD (p = 0.0049, AUC = 0.791)."}, {"asset": "source:pmid:37047493", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The high-risk score was associated with a poorer prognosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A seven-gene m6A/m5C risk model comprising METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7 stratified early-stage LUAD prognosis with p = 0.0049 and AUC = 0.791, with high risk associated with poorer prognosis.", "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:37047493"], "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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