Dataset Information

Analysis of long non-coding RNA expression profiles in gastric cancer.

ABSTRACT: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer.Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P-values below 0.01 were considered differentially expressed. An independent data set was used to validate the results.With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P-value < 0.01) with the same direction.We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.

SUBMITTER: Cao WJ

PROVIDER: S-EPMC3691033 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Analysis of long non-coding RNA expression profiles in gastric cancer.

Cao Wei-Jun WJ Wu Hai-Lu HL He Bang-Shun BS Zhang Yu-Shu YS Zhang Zhen-Yu ZY

World journal of gastroenterology 20130601 23

<h4>Aim</h4>To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer.<h4>Methods</h4>Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetri ...[more]

PMID: 23801869

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Project description:Long non-coding RNAs (lncRNAs) serve a crucial role in every aspect of cell biological functions as well as in a variety of diseases, including cardiovascular disease, cancer and nervous system disease. However, the differential expression profiles of lncRNAs in Marfan syndrome (MFS) have not been reported. The aim of the present study was to identify potential target genes behind the pathogenesis of MFS by analyzing microarray profiles of lncRNA in aortic tissues from individuals with MFS and normal aortas (NA). The differentially expressed lncRNA profiles between MFS (n=3) and NA (n=4) tissues were analyzed using microarrays. Bioinformatics analyses were used to further investigate the candidate lncRNAs. Reverse transcription-quantitative (RT-qPCR) was applied to validate the results. In total, the present study identified 294 lncRNAs (245 upregulated and 49 downregulated) and 644 mRNAs (455 upregulated and 189 downregulated) which were differential expressed between MFS and NA tissues (fold change ≥1.5; P<0.05). Gene Ontology enrichment analysis indicated that the differentially expressed mRNAs were involved in cell adhesion, elastic fiber assembly, extracellular matrix (ECM) organization, the response to virus and the inflammatory response. Kyoto Encyclopedia of Gene and Genomes pathway analysis indicated that the differentially expressed mRNAs were mainly associated with focal adhesion, the ECM-receptor interaction, the mitogen-activated protein kinase signaling pathway and the tumor necrosis factor signaling pathway. The lncRNA-mRNA coexpression network analysis further elucidated the interaction between the lncRNAs and mRNAs. A total of five lncRNAs (uc003jka.1, uc003jox.1, X-inactive specific transcript, linc-lysophosphatidic acid receptor 1 and linc-peptidylprolyl isomerase domain and WD repeat containing 1) with the highest degree of coexpression were selected and confirmed using RT-qPCR. In the present study, expression profiles of lncRNA and mRNA in MFS were revealed using microarray analysis. These results provided novel candidates for further investigation of the molecular mechanisms and effective targeted therapies for MFS.

Project description:Although Helicobacter pylori (H.pylori) is the dominant gastrointestinal pathogen, the genetic and molecular mechanisms underlying H.pylori-related diseases have not been fully elucidated. Long non-coding RNAs (lncRNAs) have been identified in eukaryotic cells, many of which play important roles in regulating biological processes and pathogenesis. However, the expression changes of lncRNAs in human infected by H.pylori have been rarely reported. This study aimed to identify the dysregulated lncRNAs in human gastric epithelial cells and tissues infected with H.pylori.The aberrant expression profiles of lncRNAs and mRNAs in GES-1 cells with or without H.pylori infection were explored by microarray analysis. LncRNA-mRNA co-expression network was constructed based on Pearson correlation analysis. Gene Ontology (GO) and KEGG Pathway analyses of aberrantly expressed mRNAs were performed to identify the related biological functions and pathologic pathways. The expression changes of target lncRNAs were validated by qRT-PCR to confirm the microarray data in both cells and clinical specimens.Three hundred three lncRNAs and 565 mRNAs were identified as aberrantly expressed transcripts (?2 or ?0.5-fold change, P < 0.05) in cells with H.pylori infection compared to controls. LncRNA-mRNA co-expression network showed the core lncRNAs/mRNAs which might play important roles in H.pylori-related pathogenesis. GO and KEGG analyses have indicated that the functions of aberrantly expressed mRNAs in H.pylori infection were related closely with inflammation and carcinogenesis. QRT-PCR data confirmed the expression pattern of 8 (n345630, XLOC_004787, n378726, LINC00473, XLOC_005517, LINC00152, XLOC_13370, and n408024) lncRNAs in infected cells. Additionally, four down-regulated (n345630, XLOC_004787, n378726, and LINC00473) lncRNAs were verified in H.pylori-positive gastric samples.Our study provided a preliminary exploration of lncRNAs expression profiles in H.pylori-infected cells by microarray. These dysregulated lncRNAs might contribute to the pathological processes during H.pylori infection.

Project description:Gastric cancer (GC) is a common type of cancer, and identification of novel diagnostic biomarkers associated with this disease is important. The present study aimed to identify novel diagnostic biomarkers associated with the prognosis of GC, using an integrated bioinformatics approach. Differentially expressed long non-coding RNAs (lncRNAs) associated with GC were identified using Gene Expression Omnibus datasets (GSE58828, GSE72305 and GSE99416) and The Cancer Genome Atlas database. A competing endogenous RNA network that incorporated five lncRNAs [long intergenic non-protein coding RNA 501 (LINC00501), LINC00365, SOX21 antisense divergent transcript 1 (SOX21-AS1), GK intronic transcript 1 (GK-IT1) and DLEU7 antisense RNA 1 (DLEU7-AS1)], 29 microRNAs and 114 mRNAs was constructed. Gene Ontology and protein-protein interaction network analyses revealed that these lncRNAs may be involved in 'biological regulation', 'metabolic process', 'cell communication', 'developmental process', 'cell proliferation', 'reproduction' and the 'cell cycle'. The results of receiver operating characteristic curve analysis demonstrated that LINC00501 (AUC=0.819), LINC00365 (AUC=0.580), SOX21-AS1 (AUC=0.736), GK-IT1 (AUC=0.823) and DLEU7-AS1 (AUC=0.932) had the potential to become valuable diagnostic biomarkers for GC. Associations with clinicopathological characteristics demonstrated that LINC00501 expression was significantly associated with sex (P=0.015) and tumor grade (P=0.022). Furthermore, LINC00365 expression was significantly associated with lymph node metastasis (P=0.025). Gene set enrichment analysis revealed that LINC00501, LINC00365 and SOX21-AS1 were enriched in signaling pathways associated with GC. Reverse transcription-quantitative PCR analysis demonstrated that LINC00501 expression (P=0.043) was significantly upregulated in GC tissues, whereas the expression levels of LINC00365 (P=0.033) and SOX21-AS1 (P=0.037) were significantly downregulated in GC tissues. Taken together, the results of the present study suggest that LINC00501, LINC00365, SOX21-AS1, GK-IT1 and DLEU7-AS1 may be used as novel diagnostic biomarkers for GC, and may be functionally associated with GC development and progression.

Project description:BACKGROUND: Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome yet their potential roles in human cancers are not well understood. The aim of the present study was to determine the lncRNA expression profile in gastric cancer and its potential clinical value. METHODS: The global lncRNA expression profile in gastric cancer was measured by lncRNA microarray. Levels of two representative lncRNAs, H19 and uc001lsz, were confirmed by real-time reverse transcriptase-polymerase chain reaction. The relationship between their levels and clinicopathological factors of patients with gastric cancer was explored. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases. RESULTS: Total of 135 lncRNAs, which differential expression levels between tumor and non-tumorous tissues were more than twofold, were found (GEO No. GSE47850). The most down-regulated lncRNAs in gastric cancer tissues were FER1L4, uc001lsz, BG491697, AF131784, uc009ycs, BG981369, AF147447, HMlincRNA1600, and AK054588; while the most up-regulated ones were H19, HMlincRNA717, BM709340, BQ213083, AK054978, and DB077273. H19 was found highly expressed in stomach and liver cancer cell lines, while lowly expressed in lung cancer and prostate cancer cell lines. Uc001lsz was lowly expressed in gastric, lung and liver cancer cell lines, while highly expressed in prostate cancer. The areas under ROC curves were up to 0.613, 0.751, and 0.761 for H19, uc001lsz, and the combination, respectively. CONCLUSIONS: The lncRNA expression profile in gastric cancer suggests the potential roles of lncRNAs in gastric cancer occurrence and development. The overexpression of H19 in gastric cancer suggests that H19 may be participated in gastric cancer. The reduced expression of uc001lsz in gastric cancer cell lines and tissues, its associations with TNM stage, and its dysregulation in early cancer and precancerous lesions suggest that uc001lsz may be a potential marker for the diagnosis of early gastric cancer.

Dataset Information

Analysis of long non-coding RNA expression profiles in gastric cancer.

Publications

Analysis of long non-coding RNA expression profiles in gastric cancer.

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