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pmid:34126961
Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis.
Xiao-Qing Lu · Jia-Qian Zhang · Sheng-Xiao Zhang · Jun Qiao · Meng-Ting Qiu · Xiang-Rong Liu · Xiao-Xia Chen · Chong Gao · Huan-Hu Zhang
BMC cancer · 2021 doi:10.1186/s12885-021-08358-7
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Complete file
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Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy.\nMETHODS: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan-Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs.\nRESULTS: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients.\nCONCLUSIONS: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.", "claims": [{"id": "claim-method", "statement": "Then the statistically significant DEGs was selected by Moderated T statistic approach with “limma [8]” and “oligo [9]” package of Bioconductor. 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"version": null, "note": "Primer sequences of PCR", "structure": {"pmcid": "PMC8201699", "section_index": 10, "section_title": "Validation of selected DEGs’ transcription in fresh GC tissue specimens using quantitative real-time PCR", "row_count": 9, "column_count": 3}, "table": {"label": "Table 1", "caption": "Primer sequences of PCR", "rows": [["gene", "Forward primer(5–3)", "Reverse primer(5–3)"], ["HMMR", "GCTAAGCAAGAAGGCATGGA", "CCACTTGATCTGAAGCACAAC"], ["SPP1", "GCCGAGGTGATAGTGTGGTT", "AACGGGGATGGCCTTGTATG"], ["FN1", "AATAGATGCAACGATCAGGACA", "GCAGGTTTCCTCGATTATCCTT"], ["CCNB1", "GACTTTGCTTTTGTGACTGACA", "CCCAGACCAAAGTTTAAAGCTC"], ["CXCL8", "AACTGAGAGTGATTGAGAGTGG", "ATGAATTCTCAGCCCTCTTCAA"], ["MAD2L1", "ACGGTGACATTTCTGCCACT", "TGGTCCCGACTCTTCCCATT"], ["CCNA2", "AGAAACAGCCAGACATCACTAA", "TTCAAACTTTGAGGCTAACAGC"], ["GAPDH", "ACAGTCAGCCGCATCTTCTT", "ACGACCAAATCCGTTGACTC"]], "row_count": 9, "column_count": 3, "numeric_cells": 2, "header_rows": 1, "locator": "section[10]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34126961:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ac153d28342e87083d5d90f42ae7c976f83262e1f5e87f63fb86d9374ed59615", "bytes": 1614, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#Tab2", "version": null, "note": "Details of seven selected genes", "structure": {"pmcid": "PMC8201699", "section_index": 15, "section_title": "Identification of the selected genes", "row_count": 8, "column_count": 4}, "table": {"label": "Table 2", "caption": "Details of seven selected genes", "rows": [["N", "Gene symbol", "Full name", "Function"], ["1", "HMMR", "hyaluronan mediated motility receptor", "the driver of tumor progression, plays a important role in the modulation of motor activities and the maintenance of genome stability."], ["2", "SPP1", "secreted phosphoprotein 1", "The protein encoded by this gene is involved in the attachment of osteoclasts to the mineralized bone matrix"], ["3", "FN1", "fibronectin 1", "Fibronectin 1 (FN1) is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, metastasis, and implicated in various biochemical processes."], ["4", "CCNB1", "cyclin B1", "an important regulator in cell cycle machinery, is a monitoring protein in mitosis and expressed primarily in G2/M phase which is critical for controlling the cell cycle at the G2/M (mitosis) transition"], ["5", "CXCL8", "C-X-C motif chemokine ligand 8", "a chemokine that acts as an important multifunctional cytokine to modulate tumour proliferation, invasion and migration in an autocrine or paracrine manner."], ["6", "MAD2L1", "mitotic arrest deficient 2 like 1", "a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate"], ["7", "CCNA2", "cyclin A2", "The protein encoded by this gene belongs to the highly conserved cyclin family, whose members function as regulators of the cell cycle."]], "row_count": 8, "column_count": 4, "numeric_cells": 12, "header_rows": 1, "locator": "section[15]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:34126961:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:417fba7045466501ae80dad9a3e487634cf2c7c1b6a6f729c9391b54a3a4a073", "bytes": 3090, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#Tab3", "version": null, "note": "Analysis of 7 selected genes by GO and KEGG pathway enrichment. FDR, false discovery rate. GO, gene ontology; BP, biological process, CC, cellular component; MF, molecular function; KEGG, Kyoto Encyclopedia of Genes and Genomes; DEMs, differentially expressed miRNAs", "structure": {"pmcid": "PMC8201699", "section_index": 18, "section_title": "Analysis of 7 selected genes via gene ontology and pathway enrichment", "row_count": 22, "column_count": 7}, "table": {"label": "Table 3", "caption": "Analysis of 7 selected genes by GO and KEGG pathway enrichment. FDR, false discovery rate. GO, gene ontology; BP, biological process, CC, cellular component; MF, molecular function; KEGG, Kyoto Encyclopedia of Genes and Genomes; DEMs, differentially expressed miRNAs", "rows": [["Category", "Term", "Count", "%", "PValue", "Genes", "FDR"], ["GOTERM_BP_DIRECT", "GO:0048146 ~ positive regulation of fibroblast proliferation", "3", "0.263", "1.51E-04", "CCNB1, CCNA2, FN1", "0.174735"], ["GOTERM_BP_DIRECT", "GO:0051301 ~ cell division", "3", "0.263", "0.006147477", "CCNB1, MAD2L1, CCNA2", "6.892135"], ["GOTERM_BP_DIRECT", "GO:0051436 ~ negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle", "2", "0.175", "0.025106263", "CCNB1, MAD2L1", "25.50655"], ["GOTERM_BP_DIRECT", "GO:0051437 ~ positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition", "2", "0.175", "0.026854324", "CCNB1, MAD2L1", "27.03882"], ["GOTERM_BP_DIRECT", "GO:0022617 ~ extracellular matrix disassembly", "2", "0.175", "0.026854324", "SPP1, FN1", "27.03882"], ["GOTERM_BP_DIRECT", "GO:0031145 ~ anaphase-promoting complex-dependent catabolic process", "2", "0.175", "0.027901906", "CCNB1, MAD2L1", "27.94322"], ["GOTERM_BP_DIRECT", "GO:0071456 ~ cellular response to hypoxia", "2", "0.175", "0.033820471", "CCNB1, CCNA2", "32.86331"], ["GOTERM_BP_DIRECT", "GO:0000086 ~ G2/M transition of mitotic cell cycle", "2", "0.175", "0.047971221", "CCNB1, HMMR", "43.40814"], ["GOTERM_BP_DIRECT", "GO:0042787 ~ protein ubiquitination involved in ubiquitin-dependent protein catabolic process", "2", "0.175", "0.053446406", "CCNB1, MAD2L1", "47.06463"], ["GOTERM_BP_DIRECT", "GO:0030198 ~ extracellular matrix organization", "2", "0.175", "0.068031098", "SPP1, FN1", "55.77698"], ["GOTERM_BP_DIRECT", "GO:0001525 ~ angiogenesis", "2", "0.175", "0.077092848", "CXCL8, FN1", "60.50819"], ["GOTERM_CC_DIRECT", "GO:0000922 ~ spindle pole", "2", "0.175", "0.035359174", "CCNB1, MAD2L1", "26.96429"], ["GOTERM_CC_DIRECT", "GO:0005615 ~ extracellular space", "3", "0.263", "0.067058677", "CXCL8, SPP1, FN1", "45.44016"], ["GOTERM_CC_DIRECT", "GO:0005576 ~ extracellular region", "3", "0.263", "0.092078284", "CXCL8, SPP1, FN1", "56.9647"], ["GOTERM_MF_DIRECT", "GO:0005515 ~ protein binding", "7", "0.613", "0.019847501", "CCNB1, MAD2L1, CXCL8, CCNA2, SPP1, FN1, HMMR", "13.51086"], ["KEGG_PATHWAY", "hsa04512:ECM-receptor interaction", "3", "0.263", "0.002294922", "SPP1, FN1, HMMR", "2.054976"], ["KEGG_PATHWAY", "hsa04914:Progesterone-mediated oocyte maturation", "3", "0.263", "0.002294922", "CCNB1, MAD2L1, CCNA2", "2.054976"], ["KEGG_PATHWAY", "hsa04110:Cell cycle", "3", "0.263", "0.004611117", "CCNB1, MAD2L1, CCNA2", "4.090835"], ["KEGG_PATHWAY", "hsa05146:Amoebiasis", "2", "0.175", "0.088997082", "CXCL8, FN1", "56.93087"], ["KEGG_PATHWAY", "hsa04620:Toll-like receptor signaling pathway", "2", "0.175", "0.088997082", "CXCL8, SPP1", "56.93087"], ["KEGG_PATHWAY", "hsa04114:Oocyte meiosis", "2", "0.175", "0.093026279", "CCNB1, MAD2L1", "58.62208"]], "row_count": 22, "column_count": 7, "numeric_cells": 105, "header_rows": 1, "locator": "section[18]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:E-MTAB-1440 not downloaded", "asset:data:geo:E-MTAB-1440 licence not read", "asset:data:geo:GSE13911 not downloaded", "asset:data:geo:GSE13911 licence not read", "asset:data:geo:GSE19826 not downloaded", "asset:data:geo:GSE19826 licence not read", "asset:data:geo:GSE27342 not downloaded", "asset:data:geo:GSE27342 licence not read", "asset:data:geo:GSE33335 not downloaded", "asset:data:geo:GSE33335 licence not read", "asset:data:geo:GSE56807 not downloaded", "asset:data:geo:GSE56807 licence not read", "asset:data:geo:GSE79973 not downloaded", "asset:data:geo:GSE79973 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"fdr_threshold": "with Benjamini–Hochberg false discovery rate adjustment"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "reordered", "quote": "Then the statistically significant DEGs was selected by Moderated T statistic approach with “limma [8]” and “oligo [9]” package of Bioconductor. 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