Dataset Information

Screening for the Key lncRNA Targets Associated With Metastasis of Renal Clear Cell Carcinoma.

ABSTRACT: A large number of long noncoding RNAs (lncRNAs) have been found to be implicated in varieties of tumors. However, the contributions of lncRNAs to tumorigenesis in renal clear cell carcinoma (RCCC) remain largely unknown.We performed a genome-wide analysis of lncRNA expression in RCCC and matched nontumor (NT) tissues to identify new targets for further study of renal carcinoma.The genome-wide analysis of lncRNA expression in 3 RCCC and matched NT tissues were conducted using 4 × 180K Agilent lncRNA Chips and 6 lncRNAs were selected and validated by qRT-PCR in 90 RCCC patients. The differentially expressed lncRNAs and mRNAs were recognized through P value and fold-change (FC) filtering. Potential targets associated with RCCC were identified by gene ontology and pathway analyses. Construction of the co-expression network was accomplished using Cytoscape.A total of 3862 lncRNAs and 2935 mRNAs were deregulated in RCCC tissues, compared with paired NT tissues. PCR results showed the expressions of these 6 lncRNAs were consistent with the chips. Moreover, the co-expression network analysis portended 641 nodes and 571 connections between 109 lncRNAs and 532 coding genes. Lastly, NONHSAT123350 could be involved in the pathogenesis of RCCC and its expression level was closely related to disease-free survival (DFS) and overall survival (OS) in patients without distant metastasis.Our results indicated that these abnormal lncRNAs could respond to renal carcinoma progression and NONHSAT123350 may act as a potential target for future treatment of RCCC.

SUBMITTER: Liu H

PROVIDER: S-EPMC4718294 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Screening for the Key lncRNA Targets Associated With Metastasis of Renal Clear Cell Carcinoma.

Liu Huibin H Chen Peng P Jiang Chunyang C Han Jing J Zhao Bing B Ma Yujiao Y Mardan Mahmut M

Medicine 20160101 2

A large number of long noncoding RNAs (lncRNAs) have been found to be implicated in varieties of tumors. However, the contributions of lncRNAs to tumorigenesis in renal clear cell carcinoma (RCCC) remain largely unknown.We performed a genome-wide analysis of lncRNA expression in RCCC and matched nontumor (NT) tissues to identify new targets for further study of renal carcinoma.The genome-wide analysis of lncRNA expression in 3 RCCC and matched NT tissues were conducted using 4 × 180K Agilent lnc ...[more]

PMID: 26765468

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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC metastasis remains unknown.MethodsDifferentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (n = 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1).ResultsA total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (PCOLCE), prolyl 4-hydroxylase subunit beta (P4HB), collagen type VI alpha 2 (COL6A2) and collagen type VI alpha 3 (COL6A3). Patients with higher expression of these key genes had worse survival than those with lower expression. In vitro experiments revealed that the mRNA expression levels of PCOLCE, P4HB and COL6A2 were three times higher and that of COL6A3 mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance.ConclusionPCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.

Project description:Clear cell renal cell carcinoma (ccRCC) is a common malignancy with high distant metastasis rate. Long non-coding RNAs (LncRNAs) are reported to be upregulated or downregulated in multiple cancers and play a crucial role in the metastasis of tumors or prognosis. Therefore, the purpose of our study is to construct a prognostic signature for ccRCC based on distant metastasis-related lncRNAs and explore the involved potential competitive endogenous RNA (ceRNA) network. The differentially expressed genes (DEGs) screened from the database of the cancer genome atlas (TCGA) were used to construct a co-expression network and identify the distant metastasis-related module by weighted gene co-expression network analysis (WGCNA). Key genes with metastatic and prognostic significance were identified through rigorous screening, including survival analysis, correlation analysis, and expression analyses in stage, grade, and distant metastasis, and were verified in the data set of gene expression omnibus (GEO) and the database from gene expression profiling interactive analysis (GEPIA). The potential upstream miRNAs and lncRNAs were predicted via five online databases and LncBase. Here, we constructed a ceRNA network of key genes that are significantly associated with the distant metastasis and prognosis of patients with ccRCC. The distant metastasis-related lncRNAs were used to construct a risk score model through the univariate, least absolute shrinkage selection operator (LASSO), and multivariate Cox regression analyses, and the patients were divided into high- and low-risk groups according to the median of the risk score. The Kaplan-Meier survival analysis demonstrated that mortality was significantly higher in the high-risk group than in the low-risk group. Considering the other clinical phenotype, the Cox regression analyses indicated that the lncRNAs model could function as an independent prognostic factor. Quantitative real-time (qRT)-PCR in the tissues and cells of ccRCC verified the high-expression level of three lncRNAs. Gene set enrichment analysis (GSEA) revealed that the lncRNA prognostic signature was mainly enriched in autophagy- and immune-related pathways, indicating that the autophagy and immune functions may play an important role in the distant metastasis of ccRCC. In summary, the constructed distant metastasis-related lncRNA signature could independently predict prognosis in patients with ccRCC, and the related ceRNA network provided a new sight on the potential mechanism of distant metastasis and a promising therapeutic target for ccRCC.

Dataset Information

Screening for the Key lncRNA Targets Associated With Metastasis of Renal Clear Cell Carcinoma.

Publications

Screening for the Key lncRNA Targets Associated With Metastasis of Renal Clear Cell Carcinoma.

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