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pmid:39309865
Eight types of RNA modification regulators define clinical outcome and immune response in gastric cancer.
Danhong Dong · Pengfei Yu · Xin Guo · Jinqiang Liu · Xisheng Yang · Gang Ji · Xiaohua Li · Jiangpeng Wei
Heliyon · 2024 doi:10.1016/j.heliyon.2024.e37076
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Numerous studies indicate that the dysregulation of these RNA modifications is linked to cancer development and may offer new therapeutic avenues for treatment. In our research, we focused on eight specific genes associated with RNA modifications (RMRGs) to comprehensively analyze their distinct functions in gastric cancer (GC). Furthermore, we aimed to elucidate the roles of RMRGs concerning clinicopathological characteristics, tumor microenvironment, and patient prognosis.\nMethods: In this study, we examined the expression and mutations of RMRGs in gastric cancer (GC) using data from TCGA-STAD (The Cancer Genome Atlas; Stomach adenocarcinoma) and the gene expression omnibus (GSE66229). We identified two subtypes of RMRGs and three gene clusters through consensus clustering analysis, assessing their differences in prognosis and immune cell infiltration patterns. Subsequently, we developed an RMRGs score to evaluate GC prognosis and highlight general immune features within the tumor microenvironment (TME). Lastly, we focused on MAMDC2 to validate its expression in GC and explore the effects of a MAMDC2 inhibitor on GC tumor cells.\nResults: We discovered 94 differentially expressed RMRGs common to both the TCGA-STAD and GEO datasets. Notable differences in prognosis and immune cell infiltration were observed between the two RMRGs subtypes and three gene clusters. The RMRGs score emerged as an independent prognostic factor related to the tumor microenvironment (TME) characteristics in gastric cancer (GC). Reducing MAMDC2 levels enhanced cell migration and invasion while decreasing proliferation in vitro.\nConclusions: In conclusion, this study comprehensively analyzed the role of RMRGs on GC. Our study firstly proposed RMRGs score and demonstrated its potential to be biomarkers for prognosis and immune characteristics. 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[], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-5", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-6", "family": "model_calibration", "specific": "decision_curve", "label": "Model calibration / clinical utility", "dsl_operations": ["calibration_bins", "net_benefit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictions_and_outcomes"], "evidence": {"score": 0.8, "band": "high", "quote": "decision curve analysis"}}, {"id": "method-7", "family": null, "specific": null, "label": "Consensus clustering analysis using the ConsensusCluster-Plus package, applied to merged TCGA-STAD, GSE84437, and GSE62254 expression data.", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Using the expression profiles of DE-RMRGs in the merged datasets, we applied the consensus clustering method via the ‘ConsensusCluster-Plus’ package in R software to estimate unsupervised classes of STAD samples, yielding two distinct RNA modification patterns."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE66229", "GSE62254", "GSE84437"], "resolved_accessions": ["GSE66229", "GSE62254", "GSE84437"], "statements": ["All data come from the publicly available datasets in present study. These datasets can be found here: TCGA database (http://cancergenome.nih.gov/), the GEO database (GSE66229) (GSE62254) (GSE84437) were included in this study, MSigDB datasets (http://www.gsea-msigdb.org/gsea/msigdb/index.jsp)."], "basis": "The paper names GSE66229, GSE62254, GSE84437 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:39309865", "data:geo:GSE62254"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE62254"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:32:36Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13622, "completion_tokens": 2605, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:39309865", "type": "paper", "label": "pmid:39309865"}, {"id": "source:pmid:39309865", "type": "manuscript", "label": "PMID 39309865 full text"}, {"id": "data:geo:GSE62254", "type": "dataset", "label": "GEO GSE62254"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39309865", "type": "paper", "label": "pmid:39309865"}, {"id": "source:pmid:39309865", "type": "manuscript", "label": "PMID 39309865 full text"}, {"id": "data:geo:GSE62254", "type": "dataset", "label": "GEO GSE62254"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39309865", "type": "extraction", "used": ["source:pmid:39309865"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE62254", "type": "accession_resolution", "used": ["data:geo:GSE62254"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:39309865", "parent_hash": "sha256:6038184854d7e74102f4e0089cd125dc4b3860f4393e14342223ed92f67d34b3", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE62254 licence not read", "asset:data:geo:GSE62254 not downloaded", "asset:data:geo:GSE66229 licence not read", "asset:data:geo:GSE66229 not downloaded", "asset:data:geo:GSE84437 licence not read", "asset:data:geo:GSE84437 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Kaplan-Meier"], "order_basis": "analysis_only", "id": "assay:1"}]}