CrossHub: a tool for multi-way analysis of The Cancer Genome Atlas (TCGA) in the context of gene expression regulation mechanisms

Krasnov, George S.; Dmitriev, Alexey A.; Melnikova, N. V.; Zaretsky, Andrew R.; Nasedkina, T. V.; Заседателев, А. С.; Senchenko, V. N.; Kudryavtseva, Anna V.

doi:10.1093/nar/gkv1478

Cited by 34 publications

(19 citation statements)

References 92 publications

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“…TCGA ( http://cancergenome.nih.gov ) data portal is one of the largest available public resources offering genomic, transcriptomic, methylomic, and copy number variation datasets for more than 20 cancer types. 22 , 23 We evaluated the TCGA survival of patients with PC in two online analysis websites, cBioPortal for Cancer Genomics 24 , 25 ( http://www.cbioportal.org/ ) and OncoLnc 26 ( http://www.oncolnc.org/ ), which link to the TCGA database.…”

Section: Methodsmentioning

confidence: 99%

Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases

Xie¹,

Dang²,

Wei³

et al. 2017

OTT

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PurposeLong noncoding RNAs (lncRNAs) are known to function as regulators in the development and occurrence of various tumors. MALAT1 is a highly conserved lncRNA and has vital functions in diverse tumors, including pancreatic cancer (PC). However, the underlying molecular regulatory mechanism involved in the occurrence and development of PC remains largely unknown. Thus, it is important to explore MALAT1 in PC and elucidate its function, which might offer a new perspective for clinical diagnosis and therapy.MethodsFirst, we used the Gene Expression Omnibus, Oncomine, and The Cancer Genome Atlas databases to determine the clinical diagnostic and prognostic values of MALAT1. We next used our own GeneChip and The Cancer Genome Atlas database to collect the possible target genes of MALAT1 and further utilized a bioinformatics analysis to explore the underlying significant pathways that might be crucial in PC. Finally, we identified several key target genes of MALAT1 and hope to offer references for future research.ResultsWe found that the expression of MALAT1 was significantly elevated in patients with PC. A receiver operating characteristics curve analysis showed a moderate diagnostic value (area under the curve =0.75, sensitivity =0.66, specificity =0.72). A total of 224 important overlapping genes were collected, and six hub genes (CCND1, MAPK8, VEGFA, FOS, CDH1, and HSP90AA1) were identified, of which CCND1, MAPK8, and VEGFA, are important genes in PC. Several pathways, including the mTOR signaling pathway, pathways in cancer, and the MAPK signaling pathway, were suggested to be the vital MALAT1 pathways in PC.ConclusionMALAT1 is suggested to be a promising diagnostic biomarker in PC. Six hub genes (CCND1, MAPK8, VEGFA, FOS, CDH1, and HSP90AA1), and specifically CCND1, MAPK8, and VEGFA, might be key MALAT1 target genes in PC. Due to their possible clinical significance in PC, several pathways, such as the mTOR signaling pathway, pathways in cancer, and the MAPK signaling pathway, are worthy of further study.

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Section: Methodsmentioning

confidence: 99%

Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases

Xie¹,

Dang²,

Wei³

et al. 2017

OTT

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“…Pearson correlation coefficient was used to evaluate the coexpression of human genes ( p ≤ 0.001 was taken as the criterion of statistical significance). We supplemented the coexpression analysis with ENCODE ChIP-Seq data using previously developed CrossHub tool [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c‐Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection

Snezhkina

Krasnov

Lipatova

et al. 2016

Oxidative Medicine and Cellular Longevity

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Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine oxidase (SMO), which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP), and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection.

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“…We analyzed TCGA RNA-Seq datasets (read counts) for colon cancer using CrossHub software [20]. Here is a brief description of TCGA RNA-Seq Version 2 pipeline.…”

Section: Methodsmentioning

confidence: 99%

“…RSEM was used to estimate gene and transcript abundances [22]. The further analysis of read count data was performed using CrossHub [20]. Read counts were normalized with TMM (trimmed mean of M-values) method and then two expression test were performed: for two pools of samples and for paired samples only (paired samples comprise only about 10% of all TCGA samples).…”

Section: Methodsmentioning

confidence: 99%

Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer

et al. 2016

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BackgroundColorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC.ResultsUsing CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types.ConclusionsWe identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3351-5) contains supplementary material, which is available to authorized users.

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CrossHub: a tool for multi-way analysis of The Cancer Genome Atlas (TCGA) in the context of gene expression regulation mechanisms

Cited by 34 publications

References 92 publications

Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases

Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases

The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c‐Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection

Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer

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