A novel m6A/m5C/m1A/m7G-related classification and risk signature predicts prognosis and reveals immunotherapy inclination in gastric cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39145046", "kind": "science-record", "revision": 3, "content_hash": "sha256:0f51a24f7ff38518d47a3966084b24d5f9a23eb6e06cb40d8cc6a26d6e6f51f6", "created_at": "2026-11-01T20:29:15Z", "updated_at": "2026-11-01T22:12:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel m6A/m5C/m1A/m7G-related classification and risk signature predicts prognosis and reveals immunotherapy inclination in gastric cancer.", "doi": "10.21037/tcr-23-2325", "pmid": "39145046", "authors": ["Ruyue Chen", "Lixin Jiang"], "journal": "Translational cancer research", "year": 2024, "abstract": "Background: Gastric cancer (GC) is characterized by high morbidity and mortality rates, and the prognosis is not optimistic. Therefore, the search for new biomarkers is crucial. Methylation modifications in RNA modifications play a crucial role in tumors. However, the role of methylation modification of integrated m6A/m5C/m1A/m7G, in GC and its related analysis have not been reported. It still needs to be studied in depth. Our study aims to deepen our understanding of m6A/m5C/m1A/m7G methylation and potentially provide new strategies for GC treatment.\nMethods: We used TCGA-STAD (The Cancer Genome Atlas-Stomach Adenocarcinoma) as a training set and GSE84433 as a validation set to analyze and determine potential associations between m6A/m5C/m1A/m7G-related genes and clinical risk of GC. In addition, we explored the prognostic value and potential biological mechanisms of m6A/m5C/m1A/m7G-related genes in GC through consistent clustering, differential expression gene identification, enrichment analysis, and immune infiltration analysis. Finally, we constructed m6A/m5C/m1A/m7G-related risk signature (MRRS) to evaluate the correlation between risk grade and survival prognosis, drug sensitivity, and immune infiltration, and validated the validity by immunohistochemical staining.\nResults: We identified subgroups of C1, C2, and C3 patients by consensus clustering using data from 45 m6A/m5C/m1A/m7G-related genes. The three groups showed significant differences in survival, immune scores, and immune cell infiltration. We then constructed MRRS using least absolute shrinkage and selection operator (LASSO) regression analysis, including SLC5A6, FKBP10, GPC3, and GGH, which could accurately differentiate between high-/low-risk populations. Its accuracy was further validated in the validation set and immunohistochemical staining. These results suggest that m6A/m5C/m1A/m7G are closely related to the GC tumor immune microenvironment, and MRRS has good performance in predicting the survival of GC patients.\nConclusions: In this study, we highlighted the association of m6A/m5C/m1A/m7G subtypes with changes in the GC immunotumor microenvironment. We constructed and validated MRRS, which is valuable in predicting survival, immune infiltration and drug sensitivity in GC patients. This helps to deepen our understanding of m6A/m5C/m1A/m7G methylation and potentially provides new strategies for GC treatment.", "claims": [{"id": "claim-data-access", "statement": "For the training set, transcriptome information for a total of 407 TCGA-STAD (The Cancer Genome Atlas-Stomach Adenocarcinoma) cases, including 375 STAD samples and 32 normal samples, was downloaded from TCGA database (https://portal.gdc.cancer.gov/). Mutations and matched clinicopathologic data for the TCGA-STAD dataset were also obtained from the TCGA database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39145046", "locator": "sections[5] \"Data sources\" paragraph 2", "quote": "For the training set, transcriptome information for a total of 407 TCGA-STAD (The Cancer Genome Atlas-Stomach Adenocarcinoma) cases, including 375 STAD samples and 32 normal samples, was downloaded from TCGA database (https://portal.gdc.cancer.gov/). Mutations and matched clinicopathologic data for the TCGA-STAD dataset were also obtained from the TCGA database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MRRS has good performance in predicting the survival rate of GC patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39145046", "locator": "sections[19] \"The association of MRRS with prognosis\" paragraph 2", "quote": "Thus, these results suggest that MRRS has good performance in predicting the survival rate of GC patients."}, {"asset": "source:pmid:39145046", "locator": "sections[19] \"The association of MRRS with prognosis\" paragraph 2", "quote": "In the ROC analysis, the AUC values for 1, 3, and 5 years were 0.69, 0.75, and 0.75, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "MRRS has good performance in predicting the survival rate of GC patients.", "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:39145046"], "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:GSE84433"], "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:GSE84433"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39145046", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tcr-23-2325", "sha256": "sha256:b07f7e359baef15250f8aaeb48255aa4ae4e6f272dd09367801a6f5c846c91f1", "bytes": 32971, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/tcr-23-2325", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11319980", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE84433", "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=GSE84433", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE84433", "version": null, "note": "For the training set, transcriptome information for a total of 407 TCGA-STAD (The Cancer Genome Atlas-Stomach Adenocarcinoma) cases, including 375 STAD samples and 32 normal samples, was downloaded from TCGA database (https://portal.gdc.cancer.gov/). 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