5-methylcytosine RNA methylation regulators affect prognosis and tumor microenvironment in lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35402591", "kind": "science-record", "revision": 4, "content_hash": "sha256:b4f71684673d57cd1a50c3ce717f302b8e56b7beca5cc17ce36ef90b7c6a4657", "created_at": "2026-11-01T18:14:13Z", "updated_at": "2026-11-01T22:06:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "5-methylcytosine RNA methylation regulators affect prognosis and tumor microenvironment in lung adenocarcinoma.", "doi": "10.21037/atm-22-500", "pmid": "35402591", "authors": ["Taisheng Liu", "Xiaoshan Hu", "Chunxuan Lin", "Xiaoshun Shi", "Yujing He", "Jian Zhang", "Kaican Cai"], "journal": "Annals of translational medicine", "year": 2022, "abstract": "Background: Accumulating evidence has shown that 5-methylcytosinec (m5C) RNA methylation plays an essential role in tumorigenesis. However, the roles of m5C regulators in the prognosis, tumor microenvironment (TME), and immunotherapy responses of lung adenocarcinoma (LUAD) have not been fully analyzed.\nMethods: Based on 14 m5C RNA regulators, we evaluated the m5C RNA modification patterns in patients with LUAD (n=594) in The Cancer Genome Atlas (TCGA). Unsupervised clustering analysis was performed to confirm distinct m5C modification patterns. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions of differentially expressed genes (DEGs) among different m5C RNA modification patterns. An m5C signature (m5Csig) was constructed using least absolute shrinkage and selection operator (LASSO) algorithms. The GSE72094 cohort (n=442) from the Gene Expression Omnibus (GEO) was used to validate m5Csig. A receiver operating characteristic (ROC) model was constructed to evaluate the sensitivity and specificity of m5Csig. Tumor-infiltrating immune cells (TIICs) between the high- and low-risk groups were estimated using the Cell Type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm.\nResults: We identified 3 m5C RNA modification clusters. Overall survival (OS) differed among the 3 clusters. The m5Csig, including TRDMT1, NSUN1, NSUN4, NSUN7, and ALYREF, was constructed to classify patients with LUAD into high- and low-risk groups. The high-risk group, with more immune cell infiltration, had a significantly poorer OS than that the low-risk group, which was associated with better response to immune checkpoint blockade therapy.\nConclusions: The present study revealed that m5C RNA regulators play a significant role in TME regulation in LUAD. The m5Csig can predict the prognosis of patients with LUAD and might provide novel strategies for tumor immunotherapy.", "claims": [{"id": "claim-method", "statement": "A least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was carried out to construct an optimal m5Csig to predict the prognosis of patients with LUAD.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35402591", "locator": "sections[7] \"Development of the m5C regulators-related prognostic signature\" paragraph 2", "quote": "A least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was carried out to construct an optimal m5Csig to predict the prognosis of patients with LUAD."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RNA sequencing data (n=594), somatic mutation information (n=561), copy number variation (CNV) information (n=555), and the corresponding clinicopathological features (n=522) of patients with LUAD were downloaded from TCGA (https://portal.gdc.cancer.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35402591", "locator": "sections[3] \"Acquisition of data\" paragraph 2", "quote": "The RNA sequencing data (n=594), somatic mutation information (n=561), copy number variation (CNV) information (n=555), and the corresponding clinicopathological features (n=522) of patients with LUAD were downloaded from TCGA (https://portal.gdc.cancer.gov/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three m5C RNA modification clusters were identified, with overall survival differing among the clusters.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35402591", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 3 m5C RNA modification clusters. Overall survival (OS) differed among the 3 clusters."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Three m5C RNA modification clusters were identified, with overall survival differing among the clusters.", "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:35402591"], "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:35402591", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-22-500", "sha256": "sha256:d96dc8c4dd00a19109ec1da38128709bc1f2bf5d37cfe4ef61a6e7dcae59283f", "bytes": 44831, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/atm-22-500", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8987885", "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 RNA sequencing data (n=594), somatic mutation information (n=561), copy number variation (CNV) information (n=555), and the 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