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pmid:31059106
Signature microRNAs and long noncoding RNAs in laryngeal cancer recurrence identified using a competing endogenous RNA network.
Zhengyi Tang · Ganguan Wei · Longcheng Zhang · Zhiwen Xu
Molecular medicine reports · 2019 doi:10.3892/mmr.2019.10143
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Complete file
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Datasets of recurrent and nonrecurrent laryngeal cancer samples were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GSE27020 and GSE25727) to examine differentially expressed miRNAs (DE‑miRs), lncRNAs (DE‑lncRs) and mRNAs (DEGs). miRNA‑mRNA and lncRNA‑miRNA networks were constructed by investigating the associations among these RNAs in various databases. Subsequently, the interactions identified were combined into a competing endogenous RNA (ceRNA) regulatory network. Feature genes in the miRNA‑mRNA network were identified via topological analysis and a recursive feature elimination algorithm. A support vector machine (SVM) classifier was established using the betweenness centrality values in the miRNA‑mRNA network, consisting of 32 optimal feature‑coding genes. The classification effect was tested using two validation datasets. Furthermore, coding genes in the ceRNA network were examined via pathway enrichment analyses. In total, 21 DE‑lncRs, 507 DEGs and 55 DE‑miRs were selected. The SVM classifier exhibited an accuracy of 94.05% (79/84) for sample classification prediction in the TCGA dataset, and 92.66 and 91.07% in the two validation datasets. The ceRNA regulatory network comprised 203 nodes, corresponding to mRNAs, miRNAs and lncRNAs, and 346 lines, corresponding to the interactions among RNAs. In particular, the interactions with the highest scores were HLA complex group 4 (HCG4)‑miR‑33b, HOX transcript antisense RNA (HOTAIR)‑miR‑1‑MAGE family member A2 (MAGEA2), EMX2 opposite strand/antisense RNA (EMX2OS)‑miR‑124‑calcitonin related polypeptide α (CALCA) and EMX2OS‑miR‑124‑γ‑aminobutyric acid type A receptor γ2 subunit (GABRG2). Gene enrichment analysis of the genes in the ceRNA network identified that 11 pathway terms and 16 molecular function terms were significantly enriched. 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expressed genes"], ["hsa04530", "Tight junction", "5", "0.001", "MYH1, CLDN6, MYH4, CTNNA2, CLDN10"], ["hsa04970", "Salivary secretion", "4", "0.001", "HTN3, ATP1B4, ATP1A2, STATH"], ["hsa04080", "Neuroactive ligand-receptor interaction", "6", "0.004", "GABRA2, GABRG2, PTH2R, OPRK1, CHRNA1, GRIK2"], ["hsa04918", "Thyroid hormone synthesis", "3", "0.007", "6528, ATP1B4, ATP1A2"], ["hsa04964", "Proximal tubule bicarbonate reclamation", "2", "0.008", "ATP1B4, ATP1A2"], ["hsa04960", "Aldosterone-regulated sodium reabsorption", "2", "0.020", "ATP1B4, ATP1A2"], ["hsa05033", "Nicotine addiction", "2", "0.020", "GABRA2, GABRG2"], ["hsa04973", "Carbohydrate digestion and absorption", "2", "0.025", "ATP1B4, ATP1A2"], ["hsa04670", "Leukocyte transendothelial migration", "3", "0.026", "CLDN6, CTNNA2, CLDN10"], ["hsa04978", "Mineral absorption", "2", "0.032", "ATP1B4, ATP1A2"], ["hsa04514", "Cell adhesion molecules (CAMs)", "3", "0.041", "CLDN6, NCAM2, CLDN10"]], "row_count": 12, "column_count": 5, 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"Genes"], ["GO:0006936", "Muscle contraction", "11", "4.17×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0003012", "Muscle system process", "11", "9.88×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0008015", "Blood circulation", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0003013", "Circulatory system process", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0007267", "Cell-cell signaling", "16", "9.03×10−5", "FGF5, GABRG2, GABRA2, GRIK2, OPRK1, MYLK2, ATP1A2, CXCL6, IL22, CTNNA2, CALCA, PNOC, SLC1A6, CARTPT, SLC30A8, CHRNA1"], ["GO:0006811", "Ion transport", "18", "1.32×10−4", "GABRG2, SLC5A5, GABRA2, GRIK2, ATP1B4, KCNA6, ATP1A2, TCN1, BEST3, SLC1A6, SLC5A8, LTF, ANO5, ANO4, CHRNA1, SLC30A8, SCN5A, ADD2"], ["GO:0007268", "Synaptic transmission", "11", "1.44×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0030182", "Neuron differentiation", "13", "2.09×10−4", "NCAM2, SLITRK4, SOX1, OPCML, FOXA2, PKHD1, EMX2, MDGA2, PTPRR, POU4F1, OLFM3, NEFL, CTNNA2"], ["GO:0019226", "Transmission of nerve impulse", "11", "5.20×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0055082", "Cellular chemical homeostasis", "10", "3.60×10−3", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0019725", "Cellular homeostasis", "10", "1.29×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0048878", "Chemical homeostasis", "10", "2.24×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0007155", "Cell adhesion", "12", "2.54×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2"], ["GO:0022610", "Biological adhesion", "12", "2.56×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, 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among the genes significantly differentially expressed between recurrent and nonrecurrent cancer samples.", "structure": {"pmcid": "PMC6522811", "section_index": 17, "section_title": "SVM classifier", "row_count": 33, "column_count": 5}, "table": {"label": "Table I.", "caption": "Basic information of 32 optimal feature-coding genes, among the genes significantly differentially expressed between recurrent and nonrecurrent cancer samples.", "rows": [["Gene symbol", "Betweenness centrality", "Number of interactions", "P-value", "Log2 fold-change"], ["SHISA6", "0.240", "4", "0.028", "0.544"], ["MAGEA2", "0.215", "5", "0.047", "−0.394"], ["TRDN", "0.156", "6", "0.002", "0.601"], ["RGS7", "0.149", "4", "0.001", "1.331"], ["CPNE4", "0.142", "4", "0.020", "0.657"], ["CALCA", "0.111", "3", "0.004", "1.214"], ["GABRG2", "0.101", "2", "0.035", "0.599"], ["TECRL", "0.083", "3", "0.043", "0.846"], ["MYLK2", "0.073", "3", "0.005", "0.543"], ["MYO3A", "0.058", "3", "0.048", "0.365"], ["ASB10", "0.057", "3", "0.001", "1.261"], ["WT1", "0.039", "4", "0.015", "0.712"], ["CALCB", "0.038", "2", "0.006", "0.986"], ["OPCML", "0.038", "2", "0.011", "0.693"], ["KY", "0.038", "2", "0.011", "0.502"], ["CYP3A43", "0.038", "2", "0.027", "−2.312"], ["EPHA6", "0.038", "2", "0.001", "1.216"], ["SLC6A20", "0.038", "2", "0.001", "0.583"], ["NCAM2", "0.036", "2", "0.026", "0.451"], ["FLRT3", "0.033", "2", "0.022", "0.312"], ["TMC5", "0.033", "2", "0.034", "−0.334"], ["AADACL3", "0.033", "2", "0.011", "0.983"], ["ANKRD1", "0.026", "6", "0.005", "0.520"], ["CLDN22", "0.020", "2", "0.005", "−1.662"], ["FGF5", "0.018", "2", "0.015", "0.593"], ["SCN5A", "0.016", "2", "0.009", "0.475"], ["PTPRR", "0.016", "2", "0.005", "0.561"], ["LDHC", "0.015", "2", "0.000", "−1.366"], ["OLFM3", "0.012", "2", "0.036", "1.283"], ["HRASLS5", "0.012", "2", "0.042", "−0.560"], ["SPINK6", "0.010", "2", "0.011", "−0.533"], ["SPESP1", "0.008", "2", "0.004", "0.499"]], "row_count": 33, "column_count": 5, "numeric_cells": 132, "header_rows": 1, "locator": "section[17]/table-wrap[1]#tI-mmr-19-06-4806"}}, {"id": "asset:table:pmid:31059106:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5734f893d821a46857a2bee7799ec63780011e9642e7dc1341759657ced2020e", "bytes": 638, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[2]#tII-mmr-19-06-4806", "version": null, "note": "Classifying parameters of the support vector machine classifier for the three datasets analyzed.", "structure": {"pmcid": "PMC6522811", "section_index": 17, "section_title": "SVM classifier", "row_count": 4, "column_count": 8}, "table": {"label": "Table II.", "caption": "Classifying parameters of the support vector machine classifier for the three datasets analyzed.", "rows": [["Dataset", "Number of samples", "Accuracy", "Sensitivity", "Specificity", "Positive predictive value", "Negative predictive value", "Area under receiver operating characteristic curve"], ["TCGA", "84", "0.9410", "0.947", "0.938", "0.818", "0.984", "0.986"], ["GSE27020", "109", "0.9266", "0.882", "0.947", "0.882", "0.947", "0.946"], ["GSE25727", "56", "0.9107", "0.941", "0.897", "0.8", "0.972", "0.921"]], "row_count": 4, "column_count": 8, "numeric_cells": 23, "header_rows": 1, "locator": "section[17]/table-wrap[2]#tII-mmr-19-06-4806"}}, {"id": "asset:table:pmid:31059106:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a745b59a26bbb2d9807a265a8ce64efd9ff197b00c16e681b799431bab7d5ca1", "bytes": 1238, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#tIII-mmr-19-06-4806", "version": null, "note": "Significantly enriched pathways in the competing endogenous RNA regulatory network.", "structure": {"pmcid": "PMC6522811", "section_index": 18, "section_title": "Molecular function and pathway enrichment analysis", "row_count": 12, "column_count": 5}, "table": {"label": "Table III.", "caption": "Significantly enriched pathways in the competing endogenous RNA regulatory network.", "rows": [["KEGG pathway ID", "KEGG pathway name", "Gene count", "P-value", "Differentially expressed genes"], ["hsa04530", "Tight junction", "5", "0.001", "MYH1, CLDN6, MYH4, CTNNA2, CLDN10"], ["hsa04970", "Salivary secretion", "4", "0.001", "HTN3, ATP1B4, ATP1A2, STATH"], ["hsa04080", "Neuroactive ligand-receptor interaction", "6", "0.004", "GABRA2, GABRG2, PTH2R, OPRK1, CHRNA1, GRIK2"], ["hsa04918", "Thyroid hormone synthesis", "3", "0.007", "6528, ATP1B4, ATP1A2"], ["hsa04964", "Proximal tubule bicarbonate reclamation", "2", "0.008", "ATP1B4, ATP1A2"], ["hsa04960", "Aldosterone-regulated sodium reabsorption", "2", "0.020", "ATP1B4, ATP1A2"], ["hsa05033", "Nicotine addiction", "2", "0.020", "GABRA2, GABRG2"], ["hsa04973", "Carbohydrate digestion and absorption", "2", "0.025", "ATP1B4, ATP1A2"], ["hsa04670", "Leukocyte transendothelial migration", "3", "0.026", "CLDN6, CTNNA2, CLDN10"], ["hsa04978", "Mineral absorption", "2", "0.032", "ATP1B4, ATP1A2"], ["hsa04514", "Cell adhesion molecules (CAMs)", "3", "0.041", "CLDN6, NCAM2, CLDN10"]], "row_count": 12, "column_count": 5, "numeric_cells": 37, "header_rows": 1, "locator": "section[18]/table-wrap[1]#tIII-mmr-19-06-4806"}}, {"id": "asset:table:pmid:31059106:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2df3e319f66e1ea49df05d1e0275a1306a3c496d0fda80412c2746cd42e2d9b9", "bytes": 2665, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[2]#tIV-mmr-19-06-4806", "version": null, "note": "Significantly enriched molecular functions in the competing endogenous RNA regulatory network.", "structure": {"pmcid": "PMC6522811", "section_index": 18, "section_title": "Molecular function and pathway enrichment analysis", "row_count": 17, "column_count": 5}, "table": {"label": "Table IV.", "caption": "Significantly enriched molecular functions in the competing endogenous RNA regulatory network.", "rows": [["GO term ID", "GO term name", "Gene count", "P-value", "Genes"], ["GO:0006936", "Muscle contraction", "11", "4.17×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0003012", "Muscle system process", "11", "9.88×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0008015", "Blood circulation", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0003013", "Circulatory system process", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0007267", "Cell-cell signaling", "16", "9.03×10−5", "FGF5, GABRG2, GABRA2, GRIK2, OPRK1, MYLK2, ATP1A2, CXCL6, IL22, CTNNA2, CALCA, PNOC, SLC1A6, CARTPT, SLC30A8, CHRNA1"], ["GO:0006811", "Ion transport", "18", "1.32×10−4", "GABRG2, SLC5A5, GABRA2, GRIK2, ATP1B4, KCNA6, ATP1A2, TCN1, BEST3, SLC1A6, SLC5A8, LTF, ANO5, ANO4, CHRNA1, SLC30A8, SCN5A, ADD2"], ["GO:0007268", "Synaptic transmission", "11", "1.44×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0030182", "Neuron differentiation", "13", "2.09×10−4", "NCAM2, SLITRK4, SOX1, OPCML, FOXA2, PKHD1, EMX2, MDGA2, PTPRR, POU4F1, OLFM3, NEFL, CTNNA2"], ["GO:0019226", "Transmission of nerve impulse", "11", "5.20×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0055082", "Cellular chemical homeostasis", "10", "3.60×10−3", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0019725", "Cellular homeostasis", "10", "1.29×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0048878", "Chemical homeostasis", "10", "2.24×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0007155", "Cell adhesion", "12", "2.54×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2"], ["GO:0022610", "Biological adhesion", "12", "2.56×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2"], ["GO:0050877", "Neurological system process", "17", "3.28×10−2", "GABRG2, GABRA2, MYO3A, GRIK2, OPRK1, MYLK2, ATP1A2, TAS1R1, CTNNA2, CALCA, NCAM2, PNOC, SLC1A6, CARTPT, POU4F1, CHRNA1, NEFL"], ["GO:0042592", "Homeostatic process", "12", "3.94×10−2", "CALCA, CALCB, XIRP1, GRIK2, PKHD1, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1, EPO"]], "row_count": 17, "column_count": 5, "numeric_cells": 56, "header_rows": 1, "locator": "section[18]/table-wrap[2]#tIV-mmr-19-06-4806"}}], "gaps": ["asset:data:geo:GSE25727 not downloaded", "asset:data:geo:GSE25727 licence not read", "asset:data:geo:GSE27020 not 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