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pmid:32801763
FKBP10 Acts as a New Biomarker for Prognosis and Lymph Node Metastasis of Gastric Cancer by Bioinformatics Analysis and in Vitro Experiments.
Li-Bao Gong · Chuang Zhang · Ruo-Xi Yu · Ce Li · Yi-Bo Fan · Yun-Peng Liu · Xiu-Juan Qu
OncoTargets and therapy · 2020 doi:10.2147/OTT.S253154
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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Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to identify the abnormally active pathways in patients with gastric cancer. Univariate Cox regression analysis was used to identify genes with stable prognostic value in gastric cancer patients based on three independent gastric cancer databases (GSE15459, GSE62254, TCGA-STAD). Gene set enrichment analysis (GSEA) was used to explore the possible pathways related to FKBP10. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of FKBP10 mRNA in the HGC-27 and MKN-7 cell lines. Adhesion assay was used to detect changes in cell adhesion ability. FKBP10, ITGA1, ITGA2, ITGA5, ITGAV, ITGA6, P- AKT 473, P- AKT 308, AKT, and β-actin were evaluated by Western blot (WB).\nRESULTS: We first performed differential expression genes (DEGs) screening of four independent GC databases (GSE27342, GSE29272, GSE54129 and TCGA-STAD). Eighty-nine genes showed consistent up-regulation in GC, the results of pathway analysis showed that they were related to \"Focal adhesion\". The prognostic value of these 89 genes was tested in three independent GC databases GSE15459, GSE62254 and TCGA-STAD cohort. Finally, 12 genes, in which the expression of FKBP10 was prominently increased in patients with lymph node metastasis (LNM), showed stable prognostic value. The following gene set enrichment analysis (GSEA) also showed that FKBP10 is mainly involved in cell adhesion process, while adhesion experiments confirmed that cell adhesion was down-regulated after silencing FKBP10 in GC cells, and adhesion-related molecules integrin αV and α6 were down-regulated.\nCONCLUSION: FKBP10 may be used as a marker for lymph node metastasis of GC and could be used as a potential target for future treatment of GC.", "claims": [{"id": "claim-method", "statement": "DEGs of TCGA-STAD were screened under the criteria of adj.P < 0.05 and FC ≥ 1.5 using R package “DESeq2”. 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"0.003898636"], ["KEGG_ECM_RECEPTOR_INTERACTION", "2.0214167", "0.0056926", "1.6152014", "0.017578125", "2.1009507", "0"], ["KEGG_FOCAL_ADHESION", "2.0666113", "0", "1.5525595", "0.033932135", "2.0269659", "0.002020202"], ["KEGG_GLYCOSAMINOGLYCAN_BIOSYNTHESIS_CHONDROITIN_SULFATE", "2.0582051", "0", "1.5097376", "0.046464648", "1.9965792", "0"], ["KEGG_PATHWAYS_IN_CANCER", "1.9199884", "0", "1.3536916", "0.04761905", "1.93229", "0"], ["KEGG_TGF_BETA_SIGNALING_PATHWAY", "1.7097332", "0.003824092", "1.5905491", "0.009881423", "1.957675", "0"]], "row_count": 8, "column_count": 7, "numeric_cells": 38, "header_rows": 2, "locator": "section[18]/table-wrap[1]#T0001"}}], "gaps": ["asset:data:geo:GSE15459 not downloaded", "asset:data:geo:GSE15459 licence not read", "asset:data:geo:GSE27342 not downloaded", "asset:data:geo:GSE27342 licence not read", "asset:data:geo:GSE29272 not downloaded", "asset:data:geo:GSE29272 licence not read", "asset:data:geo:GSE54129 not downloaded", "asset:data:geo:GSE54129 licence not read", "asset:data:geo:GSE62254 not downloaded", "asset:data:geo:GSE62254 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "deseq2", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs of TCGA-STAD were screened under the criteria of adj.P < 0.05 and FC ≥ 1.5 using R package “DESeq2”. DEGs of GSE29272, GSE54129, GSE27342 cohort were screened under the criteria of corrected adj.P < 0.05 and FC ≥ 1.5 using R package “limma”."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-3", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-4", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "Hierarchical clustering"}}], "targets": [], "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: deseq2."}, "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": ["GSE27342", "GSE29272", "GSE54129", "GSE15459", "GSE62254"], "resolved_accessions": ["GSE27342", "GSE29272", "GSE54129", "GSE15459", "GSE62254"], "statements": ["The RNAseq matrix and corresponding clinical information of TCGA-STAD cohort were downloaded from TCGA data portal (http://cancergenome.nih.gov/)."], "basis": "The paper names GSE27342, GSE29272, GSE54129, GSE15459, GSE62254 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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Univariate Cox regression an", "ssion of FKBP10 was prominently increased in patients with lymph node metastasis (LNM), showed stable p"], "order_basis": "paper_text_order:477", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["AKT 308, AKT, and β-actin were evaluated by Western blot (WB). 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