Transcriptional landscape of human cancers

Abstract

The homogeneity and heterogeneity in somatic mutations, copy number alterations and methylation across different cancer types have been extensively explored. However, the related exploration based on transcriptome data is lacking. In this study we explored gene expression profiles across 33 human cancer types using The Cancer Genome Atlas (TCGA) data. We identified consistently upregulated genes (such as E2F1, EZH2, FOXM1, MYBL2, PLK1, TTK, AURKA/B and BUB1) and consistently downregulated genes (such as SCARA5, MYOM1, NKAPL, PEG3, USP2, SLC5A7 and HMGCLL1) across various cancers. The dysregulation of these genes is likely to be associated with poor clinical outcomes in cancer. The dysregulated pathways commonly in cancers include cell cycle, DNA replication, repair, and recombination, Notch signaling, p53 signaling, Wnt signaling, TGFβ signaling, immune response etc. We also identified genes consistently upregulated or downregulated in highly-advanced cancers compared to lowly-advanced cancers. The highly (low) expressed genes in highly-advanced cancers are likely to have higher (lower) expression levels in cancers than in normal tissue, indicating that common gene expression perturbations drive cancer initiation and cancer progression. In addition, we identified a substantial number of genes exclusively dysregulated in a single cancer type or inconsistently dysregulated in different cancer types, demonstrating the intertumor heterogeneity. More importantly, we found a number of genes commonly dysregulated in various cancers such as PLP1, MYOM1, NKAPL and USP2 which were investigated in few cancer related studies, and thus represent our novel findings. Our study provides comprehensive portraits of transcriptional landscape of human cancers.

(−)‐Epigallocatechin‐3‐gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells

“…Significantly higher expression of EZH2 could be found in CRC tissues. This result was supported by our immunohistochemistry staining results and other bioinformatics analysis results based on 33 human cancer types in TCGA database, which showed that EZH2 was one of the consistently up‐regulated genes in tumour samples across various cancers . Moreover, another study found that RNA interference (RNAi)‐mediated intracellular EZH2 depletion led to blockade of the proliferation of CRC cells, which is consistent with our results.…”

“…This result was supported by our immunohistochemistry staining results and other bioinformatics analysis results based on 33 human cancer types in TCGA database, which showed that EZH2 was one of the consistently up-regulated genes in tumour samples across various cancers. 16 Moreover, another study found that RNA interference (RNAi)-mediated intracellular process malfunctions, resulting in uncontrolled cell proliferation. Of the nine up-regulated genes in cell cycle pathway, two key genes are CDK1 and CDC6.…”

Study of mitotic chromatin supports a model of bookmarking by histone modifications and reveals nucleosome deposition patterns

“…Conversely, most H3K27ac genome-wide studies describe a degree of locus specificity in the maintenance of H3K27ac during mitosis (Hsiung et al 2016;Li et al 2017;Liu et al 2017a;Liu et al 2017b).…”

The landscape of somatic mutation in sporadic Chinese colorectal cancer

“…Moreover, expression of PEG3 in colorectal patients shows statistically significant lower gene expression than matched controls from two independent studies using RNA-Seq and microarray platforms [26,27]. Its down expression is also reported to be statistically significant associated with patients' survival in various types of tumors [31]. PEG3 acts as a tumor suppressor gene by binding and promoting the degradation of β -catenin, which will consequently inhibit Wnt Signaling [32].…”