Dataset Information

Identifying heterogeneous subtypes of gastric cancer and subtype?specific subpaths of microRNA?target pathways.

ABSTRACT: The present study aimed to classify gastric cancer (GC) into subtypes and to screen the subtype?specific genes, their targeted microRNAs (miRNAs) and enriched pathways to explore the putative mechanism of each GC subtypes. The GSE13861 data set was downloaded from the Gene Expression Omnibus and used to screen differential expression genes (DEGs) in GC samples based on the detection of imbalanced differential signal algorithm. The specific genes in each subtype were identified with the cut?off criterion of U>0.04, pathway enrichment analysis was performed and the subtype?specific subpaths of miRNA?target pathway were determined. A total of 1,263 DEGs were identified in the primary gastric adenocarcinoma (PGD) samples, which were subsequently divided into four subtypes, according to the hierarchy cluster analysis. Identification of the subpaths of each subtype indicated that the subpath related to subtype 1 was miRNA (miR)?202/calcium voltage?gated channel subunit ?1 (CACNA1E)/type II diabetes mellitus. The nuclear factor??B signaling pathway was the most significantly specific pathway and subpath identified for subtype 2, which was regulated by miR?338?targeted suppression of C?C motif chemokine ligand 21 (CCL21). For subtype 3, significant related pathways included ubiquitin?mediated proteolysis and proteasome, and the important subpath was miR?146B/proteasome 26S subunit, non?ATPase 3 (PSMD3)/proteasome; focal adhesion was the significant pathway indicated for subtype 4, and the subpaths were miR?34A/vinculin (VCL)/focal adhesion and miR?34C/VCL/focal adhesion. In addition, Helicobacter pylori infection was higher in GC subtype 1 than in other subtypes. Specific genes, such as CACNA1E, CCL21, PSMD3 and VCL, may be used as potential feature genes to identify different subtypes of GC, and their associated subpaths may partially explain the pathogenetic mechanism of each GC subtype.

SUBMITTER: Li Y

PROVIDER: S-EPMC5802161 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Identifying heterogeneous subtypes of gastric cancer and subtype‑specific subpaths of microRNA‑target pathways.

Li Yuanhang Y Bai Weijun W Zhang Xu X

Molecular medicine reports 20171220 3

The present study aimed to classify gastric cancer (GC) into subtypes and to screen the subtype‑specific genes, their targeted microRNAs (miRNAs) and enriched pathways to explore the putative mechanism of each GC subtypes. The GSE13861 data set was downloaded from the Gene Expression Omnibus and used to screen differential expression genes (DEGs) in GC samples based on the detection of imbalanced differential signal algorithm. The specific genes in each subtype were identified with the cut‑off c ...[more]

PMID: 29286091

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Project description:Triple-negative breast cancer (TNBC) is a highly heterogeneous group of cancers, and molecular subtyping is necessary to better identify molecular-based therapies. While some classifiers have been established, no one has integrated the expression profiles of long noncoding RNAs (lncRNAs) into such subtyping criterions. Considering the emerging important role of lncRNAs in cellular processes, a novel classification integrating transcriptome profiles of both messenger RNA (mRNA) and lncRNA would help us better understand the heterogeneity of TNBC.Using human transcriptome microarrays, we analyzed the transcriptome profiles of 165 TNBC samples. We used k-means clustering and empirical cumulative distribution function to determine optimal number of TNBC subtypes. Gene Ontology (GO) and pathway analyses were applied to determine the main function of the subtype-specific genes and pathways. We conducted co-expression network analyses to identify interactions between mRNAs and lncRNAs.All of the 165 TNBC tumors were classified into four distinct clusters, including an immunomodulatory subtype (IM), a luminal androgen receptor subtype (LAR), a mesenchymal-like subtype (MES) and a basal-like and immune suppressed (BLIS) subtype. The IM subtype had high expressions of immune cell signaling and cytokine signaling genes. The LAR subtype was characterized by androgen receptor signaling. The MES subtype was enriched with growth factor signaling pathways. The BLIS subtype was characterized by down-regulation of immune response genes, activation of cell cycle, and DNA repair. Patients in this subtype experienced worse recurrence-free survival than others (log rank test, P = 0.045). Subtype-specific lncRNAs were identified, and their possible biological functions were predicted using co-expression network analyses.We developed a novel TNBC classification system integrating the expression profiles of both mRNAs and lncRNAs and determined subtype-specific lncRNAs that are potential biomarkers and targets. If further validated in a larger population, our novel classification system could facilitate patient counseling and individualize treatment of TNBC.

Dataset Information

Identifying heterogeneous subtypes of gastric cancer and subtype?specific subpaths of microRNA?target pathways.

Publications

Identifying heterogeneous subtypes of gastric cancer and subtype‑specific subpaths of microRNA‑target pathways.

Similar Datasets

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