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pmid:37161577
Establishment and verification of prognostic model and ceRNA network analysis for colorectal cancer liver metastasis.
Xuan Zhang · Tao Wu · Jinmei Zhou · Xiaoqiong Chen · Chao Dong · Zhangyou Guo · Renfang Yang · Rui Liang · Qing Feng · Ruixi Hu · Yunfeng Li · Rong Ding
BMC medical genomics · 2023 doi:10.1186/s12920-023-01523-w
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Experiment
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Complete file
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Approximately two-thirds of patients with CRC will develop colorectal cancer liver metastases (CRLM) at some point in time. In this study, we aimed to construct a prognostic model of CRLM and its competing endogenous RNA (ceRNA) network.\nMETHODS: RNA-seq of CRC, CRLM and normal samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Limma was used to obtain differential expression genes (DEGs) between CRLM and CRC from sequencing data and GSE22834, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed, respectively. Univariate Cox regression analysis and lasso Cox regression models were performed to screen prognostic gene features and construct prognostic models. Functional enrichment, estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) algorithm, single-sample gene set enrichment analysis, and ceRNA network construction were applied to explore potential mechanisms.\nRESULTS: An 8-gene prognostic model was constructed by screening 112 DEGs from TCGA and GSE22834. CRC patients in the TCGA and GSE29621 cohorts were stratified into either a high-risk group or a low-risk group. Patients with CRC in the high-risk group had a significantly poorer prognosis compared to in the low-risk group. The risk score was identified as an independent predictor of prognosis. Functional analysis revealed that the risk score was closly correlated with various immune cells and immune-related signaling pathways. And a prognostic gene-associated ceRNA network was constructed that obtained 3 prognosis gene, 14 microRNAs (miRNAs) and 7 long noncoding RNAs (lncRNAs).\nCONCLUSIONS: In conclusion, a prognostic model for CRLM identification was proposed, which could independently identify high-risk patients with low survival, suggesting a relationship between local immune status and prognosis of CRLM. Moreover, the key prognostic genes-related ceRNA network were established for the CRC investigation. Based on the differentially expressed genes between CRLM and CRC, the prognosis model of CRC patients was constructed.", "claims": [{"id": "claim-method", "statement": "The differentially expressed analysis in the sequencing data and GSE22834 was performed to screen DEGs between CRC and CRLM with |log2 fold change(FC)|> 1 and p < 0.05 as did differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in CRC and normal samples using the- “limma”-package in R [20].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37161577", "locator": "sections[5] \"Analysis of differentially expressed genes (DEGs)\" paragraph 2", "quote": "The differentially expressed analysis in the sequencing data and GSE22834 was performed to screen DEGs between CRC and CRLM with |log2 fold change(FC)|> 1 and p < 0.05 as did differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in CRC and normal samples using the- “limma”-package in R [20]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "TCGA-COAD and TCGA-READ datasets were downloaded from the TCGA (https://portal.gdc.cancer.gov/) database. GSE22834, GSE29621, GSE12945 and GSE72718 datasets were soured from the GEO (https://www.ncbi.nlm.nih.gov/geo/) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37161577", "locator": "sections[28] \"Availability of data and materials\" paragraph 2", "quote": "TCGA-COAD and TCGA-READ datasets were downloaded from the TCGA (https://portal.gdc.cancer.gov/) database. GSE22834, GSE29621, GSE12945 and GSE72718 datasets were soured from the GEO (https://www.ncbi.nlm.nih.gov/geo/) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Limma analysis of CRC and CRLM expression data identified 112 genes differentially expressed in both the authors' sequencing data and GSE22834, which were used to construct an eight-gene prognostic model.", "kind": "quantitative", "target": {"value": 2.0, "unit": "fold change", "tolerance": null, "source": "The differentially expressed analysis in the sequencing data and GSE22834 was performed to screen DEGs between CRC and CRLM with |log2 fold change(FC)|> 1 and p < 0.05 as did differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in CRC and normal samples using the- “limma”-package in R [20]."}, "evidence": [{"asset": "source:pmid:37161577", "locator": "sections[5] \"Analysis of differentially expressed genes (DEGs)\" paragraph 2", "quote": "The differentially expressed analysis in the sequencing data and GSE22834 was performed to screen DEGs between CRC and CRLM with |log2 fold change(FC)|> 1 and p < 0.05 as did differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in CRC and normal samples using the- “limma”-package in R [20]."}, {"asset": "source:pmid:37161577", "locator": "sections[14] \"Identifification of DEGs between CRC and CRLM\" paragraph 2", "quote": "After that, 112 co-DEGs between sequencing data and the GSE22834 dataset were detected and displayed by Venn graph (Fig. 1E)."}, {"asset": "source:pmid:37161577", "locator": "sections[15] \"Identification of prognosis-related DEGs and establishment of eight gene prognostic model\" paragraph 2", "quote": "Thus, Risk score = 0.0904 × APOD + 0.1861 × AKR1C1 + (− 0.2536) × TTC38 + 0.4189 × ALAD + (− 0.0505) × ALDOB + (− 0.1702) × DNASE1L3 + (− 0.0683) × SERPINA1 + 0.0865 × GRB7."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Limma analysis of CRC and CRLM expression data identified 112 genes differentially expressed in both the authors' sequencing data and GSE22834, which were used to construct an eight-gene prognostic model.", "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:37161577"], "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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No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.05, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE22834", "GSE29621", "GSE12945", "GSE72718"], "resolved_accessions": ["GSE22834", "GSE29621", "GSE12945", "GSE72718"], "statements": ["TCGA-COAD and TCGA-READ datasets were downloaded from the TCGA (https://portal.gdc.cancer.gov/) database. GSE22834, GSE29621, GSE12945 and GSE72718 datasets were soured from the GEO (https://www.ncbi.nlm.nih.gov/geo/) database."], "basis": "The paper names GSE22834, GSE29621, GSE12945, GSE72718 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37161577", "data:geo:GSE12945"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12945"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:39:09Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14346, "completion_tokens": 2525, "cached_tokens": 264}}, "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:37161577", "type": "paper", "label": "pmid:37161577"}, {"id": "source:pmid:37161577", "type": "manuscript", "label": "PMID 37161577 full text"}, {"id": "data:geo:GSE12945", "type": "dataset", "label": "GEO GSE12945"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37161577", "type": "paper", "label": "pmid:37161577"}, {"id": "source:pmid:37161577", "type": "manuscript", "label": "PMID 37161577 full text"}, {"id": "data:geo:GSE12945", "type": "dataset", "label": "GEO GSE12945"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37161577", "type": "extraction", "used": ["source:pmid:37161577"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12945", "type": "accession_resolution", "used": ["data:geo:GSE12945"], "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:37161577", "parent_hash": "sha256:d2d39e6287092ff698b7d4f650af26c742cfdb2d59355199fa08c6a46d278f99", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE12945 licence not read", "asset:data:geo:GSE12945 not downloaded", "asset:data:geo:GSE22834 licence not read", "asset:data:geo:GSE22834 not downloaded", "asset:data:geo:GSE29621 licence not read", "asset:data:geo:GSE29621 not downloaded", "asset:data:geo:GSE72718 licence not read", "asset:data:geo:GSE72718 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ing endogenous RNA (ceRNA) network. METHODS: RNA-seq of CRC, CRLM and normal samples were obtaine", "ile three pairs of samples were subjected to transcriptome sequencing. The sample information was shown"], "order_basis": "paper_text_order:401", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ile 2. Table S2: The primers of quantitative real-time PCR in the study. Additional file 3. Figure S1:"], "order_basis": "paper_text_order:3899", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The differentially expressed analysis in the sequencing data and GSE22834 was performed to screen DEGs between CRC and CRLM with |log2 fold change(FC)|> 1 and p < 0.05 as did differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in CRC and normal samples using the- “limma”-package in R [20]."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}