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pmid:35387659
Downregulation of B3GNT6 is a predictor of poor outcomes in patients with colorectal cancer.
Shihan Xiao · Chen Yang · Yang Zhang · Chen Lai
World journal of surgical oncology · 2022 doi:10.1186/s12957-022-02561-x
Paper
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Experiment
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Data
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Analysis
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Complete file
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It is generally expressed in the gastrointestinal (GI) tract; however, its clinical significance in colorectal cancer remains largely unexplored.\nMETHODS: We obtained mRNA transcriptomic sequencing data from 3 gene expression omnibus (GEO) datasets (GSE37182, GSE39582, GSE103512) and The Cancer Genome Atlas (TCGA) to compare the B3GNT6 mRNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer. We further validated this at the protein level in our cohort using immunohistochemical staining of B3GNT6 as well as the Human Protein Atlas online database.\nRESULTS: B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels. Downregulation of B3GNT6 expression was found to be associated with poor overall survival in patients with colorectal cancer as per the data in GSE39582 and TCGA databases. Low B3GNT6 mRNA levels were significantly associated with chromosome instability (CIN) and KRAS mutations in patients with colorectal cancer. Gene set enrichment analysis (GSEA) revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity.\nCONCLUSIONS: The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC. Moreover, the low expression of B3GNT6 may indicate more frequent activation of the KRAS/ERK signaling pathway, high CIN, and increased proteasomal activity. These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer.", "claims": [{"id": "claim-method", "statement": "The comparison between B3GNT6 mRNA expression levels in colorectal cancer and normal tissues from TCGA and GEO databases was performed using unpaired Student’s t tests. The diagnostic value of B3GNT6 mRNA expression was evaluated using a receiver operating characteristic (ROC) curve. Survival analysis was conducted using log-rank (Mantel-Cox) test. The association between clinicopathological characteristics and B3GNT6 mRNA expression levels was determined using the χ2 test. To determine the function of B3GNT6, we conducted GSEA using samples with top 25% and bottom 25% of B3GNT6 expression in the GSE39582 dataset with the GSEA 4.1.0 software (https://www.gsea-msigdb.org/gsea).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35387659", "locator": "sections[6] \"Statistical analysis\" paragraph 2", "quote": "The comparison between B3GNT6 mRNA expression levels in colorectal cancer and normal tissues from TCGA and GEO databases was performed using unpaired Student’s t tests."}, {"asset": "source:pmid:35387659", "locator": "sections[6] \"Statistical analysis\" paragraph 2", "quote": "The diagnostic value of B3GNT6 mRNA expression was evaluated using a receiver operating characteristic (ROC) curve."}, {"asset": "source:pmid:35387659", "locator": "sections[6] \"Statistical analysis\" paragraph 2", "quote": "Survival analysis was conducted using log-rank (Mantel-Cox) test."}, {"asset": "source:pmid:35387659", "locator": "sections[6] \"Statistical analysis\" paragraph 2", "quote": "The association between clinicopathological characteristics and B3GNT6 mRNA expression levels was determined using the χ2 test."}, {"asset": "source:pmid:35387659", "locator": "sections[4] \"Gene set enrichment analysis (GSEA)\" paragraph 2", "quote": "To determine the function of B3GNT6, we conducted GSEA using samples with top 25% and bottom 25% of B3GNT6 expression in the GSE39582 dataset with the GSEA 4.1.0 software (https://www.gsea-msigdb.org/gsea)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/), TCGA dataset (https://www.portal.gdc.cancer.gov/), MediSapiens IST Online database (http://ist.medisapiens.com/), and the Human Protein Atlas (http://www.proteinatlas.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35387659", "locator": "sections[22] \"notes\" paragraph 1", "quote": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/), TCGA dataset (https://www.portal.gdc.cancer.gov/), MediSapiens IST Online database (http://ist.medisapiens.com/), and the Human Protein Atlas (http://www.proteinatlas.org/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35387659", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "B3GNT6 expression was downregulated in colorectal cancer tissues as compared to that in the normal tissues at both mRNA and protein levels.", "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:35387659"], "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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characteristics [Expression]", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE103512 not downloaded", "asset:data:geo:GSE103512 licence not read", "asset:data:geo:GSE103582 not downloaded", "asset:data:geo:GSE103582 licence not read", "asset:data:geo:GSE37182 not downloaded", "asset:data:geo:GSE37182 licence not read", "asset:data:geo:GSE39582 not downloaded", "asset:data:geo:GSE39582 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "reordered", "quote": "The comparison between B3GNT6 mRNA expression levels in colorectal cancer and normal tissues from TCGA and GEO databases was performed using unpaired Student’s t tests. The diagnostic value of B3GNT6 mRNA expression was evaluated using a receiver operating characteristic (ROC) curve. Survival analysis was conducted using log-rank (Mantel-Cox) test. The association between clinicopathological characteristics and B3GNT6 mRNA expression levels was determined using the χ2 test. To determine the function of B3GNT6, we conducted GSEA using samples with top 25% and bottom 25% of B3GNT6 expression in the GSE39582 dataset with the GSEA 4.1.0 software (https://www.gsea-msigdb.org/gsea)."}}, {"id": "method-2", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "χ2"}}], "targets": [], "gaps": []}, "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": ["logrank_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: log_rank_test."}, "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": ["GSE37182", "GSE39582", "GSE103582", "GSE103512"], "resolved_accessions": ["GSE37182", "GSE39582", "GSE103582", "GSE103512"], "statements": ["The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/), TCGA dataset (https://www.portal.gdc.cancer.gov/), MediSapiens IST Online database (http://ist.medisapiens.com/), and the Human Protein Atlas (http://www.proteinatlas.org/)."], "basis": "The paper names GSE37182, GSE39582, GSE103582, GSE103512 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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The diagnostic value of B3GNT6 mRNA expression was evaluated using a receiver operating characteristic (ROC) curve. Survival analysis was conducted using log-rank (Mantel-Cox) test. The association between clinicopathological characteristics and B3GNT6 mRNA expression levels was determined using the χ2 test. To determine the function of B3GNT6, we conducted GSEA using samples with top 25% and bottom 25% of B3GNT6 expression in the GSE39582 dataset with the GSEA 4.1.0 software (https://www.gsea-msigdb.org/gsea)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}