Differentially expressed long non-coding RNAs and mRNAs in plasma of clear cell renal cell carcinoma patients based on microarray and bioinformatic analysis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA633809 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Objective: The diagnostic roles of long non-coding RNAs (lncRNAs) in clear cell renal cell carcinoma (ccRCC) are still not well defined. We aimed to identify differentially expressed lncRNAs and mRNAs in plasma of ccRCC patients and health controls systematically. Methods: Expression profile of lncRNAs and mRNAs in plasma from ccRCC patients and healthy controls was analyzed by microarray assay. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway based approaches were used to investigate biological functions and signaling pathways affected by the differentially expressed mRNAs. SOCS2-AS1 was selected for validation using Real-Time PCR. The differentially expressed genes were further compared with E-MTAB-1830 datasets by Venn and NetworkAnalyst website. The expression level and overall survival (OS) of differentially expressed mRNAs were analyzed in GEPIA and ULCAN website. Results: Compared with healthy controls, a total of 3,664 differentially expressed lncRNAs were revealed by heatmap and volcano-plot, including up-regulation in 1,511 and down-regulation in 2,153 (fold change ≥ 2 and P < 0.05), respectively. And differential expression was noticed in 2,268 mRNAs, including up-regulation in 932 mRNAs and down-regulation in 1,336 mRNAs, respectively (fold change ≥ 2 and P < 0.05). Pathways analysis based on deregulated mRNAs were mainly involved in melanogenesis and Hippo signaling pathway (P < 0.05). The expression of SOCS2-AS1 was down in ccRCC plasma and tissues, as well as in cell lines, which was the same as the results of lncRNA microarray. Compared with the E-MTAB-1830 gene expression profiles, we identified 18 lncRNAs, and 87 mRNAs were differently expressed in both plasma and neoplastic tissues of ccRCC. Ten mRNAs (EPB41L4B, CCND1, GGT1, CGNL1, CYSLTR1, PLAUR, UGT3A1, PROM2, MUC12, and PCK1) were correlated with the overall survival (OS) rate in ccRCC patients based on the GEPIA and ULCAN website.Conclusions: We first reported differentially expressed lncRNAs in ccRCC patient and healthy control systemically. Combined with the published dataset, we identified several differentially expressed lncRNAs and mRNAs which might to be diagnostic or prognostic markers. The biological functions of those lncRNAs and mRNAs should be further validated. Taken together, this study provided the basis for future treatment of ccRCC and novel insights into cancer biology.
2020-12-21 | GSE150833 | GEO
Project description:Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.
| S-EPMC6883955 | biostudies-literature
Project description:Objective: The roles of long non-coding RNAs (lncRNAs) in the diagnosis of clear cell renal cell carcinoma (ccRCC) are still not well-defined. We aimed to identify differentially expressed lncRNAs and mRNAs in plasma of ccRCC patients and health controls systematically. Methods: Expression profile of plasma lncRNAs and mRNAs in ccRCC patients and healthy controls was analyzed based on microarray assay. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based approaches were used to investigate biological function and signaling pathways mediated by the differentially expressed mRNAs. SOCS2-AS1 was selected for validation using Real-Time PCR. The differentially expressed lncRNAs and mRNAs were further compared with E-MTAB-1830 datasets using Venn and the NetworkAnalyst website. The GEPIA and ULCAN websites were utilized for the evaluation of the expression level of differentially expressed mRNA and their association with overall survival (OS). Results: A total of 3,664 differentially expressed lncRNAs were identified in the plasma of ccRCC patients, including 1,511 up-regulated and 2,153 down-regulated lncRNAs (fold change ?2 and P < 0.05), respectively. There were 2,268 differentially expressed mRNAs, including 932 up-regulated mRNAs and 1,336 down-regulated mRNAs, respectively (fold change ?2 and P < 0.05). Pathway analysis based on deregulated mRNAs was mainly involved in melanogenesis and Hippo signaling pathway (P < 0.05). In line with the lncRNA microarray findings, the SOCS2-AS1 was down-regulated in ccRCC plasma and tissues, as well as in cell lines. Compared with the E-MTAB-1830 gene expression profiles, we identified 18 lncRNAs and 87 mRNAs differently expressed in both plasma and neoplastic tissues of ccRCC. The expression of 10 mRNAs (EPB41L4B, CCND1, GGT1, CGNL1, CYSLTR1, PLAUR, UGT3A1, PROM2, MUC12, and PCK1) was correlated with the overall survival (OS) rate in ccRCC patients based on the GEPIA and ULCAN websites. Conclusions: We firstly reported differentially expressed lncRNAs in ccRCC patients and healthy controls systemically. Several differentially expressed lncRNAs and mRNAs were identified, which might serve as diagnostic or prognostic markers. The biological function of these lncRNAs and mRNAs should be further validated. Our study may contribute to the future treatment of ccRCC and provide novel insights into cancer biology.
| S-EPMC7729199 | biostudies-literature
Project description:Clear cell renal cell carcinoma (ccRCC) is the most common malignant renal epithelial tumor and also the most deadly. To identify molecular changes occurring in ccRCC, in the present study we performed a genome wide analysis of its entire complement of mRNAs. Gene and exon-level analyses were carried out by means of the Affymetrix Exon Array platform. To achieve a reliable detection of differentially expressed cassette exons we implemented a novel methodology that considered contiguous combinations of exon triplets and candidate differentially expressed cassette exons were identified when the expression level was significantly different only in the central exon of the triplet. More detailed analyses were performed for selected genes using quantitative RT-PCR and confocal laser scanning microscopy. Our analysis detected over 2,000 differentially expressed genes, and about 250 genes alternatively spliced and showed differential inclusion of specific cassette exons comparing tumor and non-tumoral tissues. We demonstrated the presence in ccRCC of an altered expression of the PTP4A3, LAMA4, KCNJ1 and TCF21 genes (at both transcript and protein level). Furthermore, we confirmed, at the mRNA level, the involvement of CAV2 and SFRP genes that have previously been identified. At exon level, among potential candidates we validated a differentially included cassette exon in DAB2 gene with a significant increase of DAB2 p96 splice variant as compared to the p67 isoform. Based on the results obtained, and their robustness according to both statistical analysis and literature surveys, we believe that a combination of gene/isoform expression signature may remarkably contribute, after suitable validation, to a more effective and reliable definition of molecular biomarkers for ccRCC early diagnosis, prognosis and prediction of therapeutic response.
| S-EPMC3806822 | biostudies-literature
Project description:In this study we performed a genome wide analysis of the entire complement of mRNAs in clear cell renal cell carcinomas (ccRCC) by means of the Affymetrix Exon Array platform. The analyses were performed both at gene and exon level. Under our parameters over 2,000 genes resulted differentially expressed, and about 250 genes resulted alternative spliced showing differential inclusion of specific cassette exons comparing tumor and non tumoral tissues.
2013-09-06 | GSE47032 | GEO
Project description:Tumor-infiltrating immune cells have been recognized to be associated with prognosis and response to immunotherapy; however, genes related to immune microenvironment of clear cell renal cell carcinoma (ccRCC) remains unclear. To better understand the effects of genes involved in immune and stromal cells on prognosis, we used Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), DAVID database and ESTMATE algorithm, and divided the patients into low and high groups according to immune (median: 1038.45) and stromal scores (median: 667.945), respectively. We found the immune scores were significantly correlated with clinicopathological parameters and overall survival (OS). Based on immune scores, 890 DEGs were significantly associated with OS among the 1433 up-regulated genes. Based on top 10 DEGs (IL10RA, FCER1G, SASH3, TIGIT, RHOH, IL12RB1, AIF1, LPXN, LAPTM5 and SP140), cases with number of up-regulated genes ≥ 5 were associated poor OS (P = 0.002). In addition, the mean differences of percentages of CD8 T cells (11.32%), CD4 memory resting T cells (-4.52%) and mast resting cells (-3.55%) between low and high immune scores were the most significant. Thus, combination of these genes might use to predict the efficacy of immunotherapy. Further analyses of these genes were warrant to explore their potential association with the prognosis of ccRCC.
| S-EPMC7540144 | biostudies-literature
Project description:We examined the role of differentially expressed autophagy-related genes (DEARGs) in clear cell Renal Cell Carcinoma (ccRCC) using high-throughput RNA-seq data from The Cancer Genome Atlas (TCGA). Cox regression analyses showed that 5 DEARGs (PRKCQ, BID, BAG1, BIRC5, and ATG16L2) correlated with overall survival (OS) and 4 DEARGs (EIF4EBP1, BAG1, ATG9B, and BIRC5) correlated with disease-free survival (DFS) in ccRCC patients. Multivariate Cox regression analysis using the OS and DFS prognostic risk models showed that expression of the nine DEARGs accurately and independently predicted the risk of disease recurrence or progression in ccRCC patients (area under curve or AUC values > 0.70; all p < 0.05). Moreover, the DEARGs accurately distinguished healthy individuals from ccRCC patients based on receiver operated characteristic (ROC) analyses (area under curve or AUC values > 0.60), suggesting their potential as diagnostic biomarkers for ccRCC. The expression of DEARGs also correlated with the drug sensitivity of ccRCC cell lines. The ccRCC cell lines were significantly sensitive to Sepantronium bromide, a drug that targets BIRC5. This makes BIRC5 a potential therapeutic target for ccRCC. Our study thus demonstrates that DEARGs are potential diagnostic and prognostic biomarkers and therapeutic targets in ccRCC.
| S-EPMC6834403 | biostudies-literature
Project description:Differentially expressed mRNAs after silencing lncRNA DDGC
| PRJNA665637 | ENA
Project description:The heterogeneity of renal cell carcinoma (RCC) subtypes reflects the cell type of origin in the nephron, with consequences for therapy and prognosis. The transcriptional cues that determine segment-specific gene expression patterns are poorly understood. We recently showed that hypertonicity in the renal medulla regulates nephron-specific gene expression. Here, we analyzed a set of 223 genes, which were identified in the present study by RNA-Seq to be differentially expressed by hypertonicity, for the prediction of cancer-specific survival (CSS). Cluster analyses of these genes showed discrimination between tumor and non-tumor samples of clear cell RCC (ccRCC). Refinement of this gene signature to a four-gene score (OSM score) through statistical analyses enabled prediction of CSS in ccRCC patients of The Cancer Genome Atlas (TCGA) (n = 436) in univariate (HR = 4.1; 95% CI: 2.78-6.07; p = 4.39 × 10-13), and multivariate analyses including primary tumor (T); regional lymph node (N); distant metastasis (M); grading (G)(p = 2.3 × 10-5). The OSM score could be validated in an independent ccRCC study (n = 52) in univariate (HR = 1.29; 95% CI = 1.05-1.59; p = 0.011) and multivariate analyses (p = 0.016). Cell culture experiments using RCC cell lines demonstrated that the expression of the tumor suppressor ELF5 could be restored by hypertonicity. The innovation of our novel gene signature is that these genes are physiologically regulated only by hypertonicity, thereby providing the possibility to be targeted for therapy.
| S-EPMC7017076 | biostudies-literature
Project description:Clear cell renal cell carcinoma (ccRCC) is a common human malignancy. Despite numerous efforts, there is still no reliable biomarker or combination of biomarkers available for daily practice. Our study was designed to explore the expression profile of messenger RNA (mRNA) and long non-coding RNA (lncRNA) transcripts in ccRCC in order to identify potential diagnostic biomarkers for patients with ccRCC. Total RNA from corresponding normal and malignant tissue of 15 patients with ccRCC was isolated. Expression profiling was performed using a custom Agilent gene expression microarray which allowed the analysis of 34,144 mRNA and 32,183 lncRNA transcripts. We observed that a subset of mRNA (n = 1064; 3.1%) and lncRNA (n = 1308; 4.1%) transcripts are dysregulated (fold change > 2) in ccRCC tissue. The relative higher number of differentially expressed lncRNAs indicates that lncRNA profiling may be better suited for diagnostic purposes; a number of so far unknown RNAs with potential diagnostic interest in ccRCC are identified by our gene expression profiling study. The data are deposited in the Gene Expression Omnibus (GSE61763).
| S-EPMC4584005 | biostudies-literature