Integrated analysis of a competing endogenous RNA network reveals a ferroptosis-related 6-lncRNA prognostic signature in clear cell renal cell carcinoma.
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引用次数: 0
Abstract
Background: Establishing a robust signature for prognostic prediction and precision treatment is necessary due to the heterogeneous prognosis and treatment response of clear cell renal cell carcinoma (ccRCC).
Objectives: This study set out to elucidate the biological functions and prognostic role of ferroptosis-related long non-coding RNAs (lncRNAs) based on a synthetic analysis of competing endogenous RNA networks in ccRCC.
Material and methods: Ferroptosis-related genes were obtained from the FerrDb database. The expression data and matched clinical information of lncRNAs, miRNAs and mRNAs from The Cancer Genome Atlas (TCGA) database were obtained to identify differentially expressed RNAs. The lncRNA-miRNA-mRNA ceRNA network was established utilizing the common miRNAs that were predicted in the RNAHybrid, StarBase and TargetScan databases. Then, using progressive univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis of gene expression data and clinical information, a ferroptosis-related lncRNA prognosis signature was constructed based on the lncRNAs in ceRNA. Finally, the influence of independent lncRNAs on ccRCC was explored.
Results: A total of 35 ferroptosis-related mRNAs, 356 lncRNAs and 132 miRNAs were sorted out after differential expression analysis in the TCGA-KIRC. Subsequently, overlapping lncRNA-miRNA and miRNA-mRNA interactions among the RNAHybrid, StarBase and TargetScan databases were constructed and identified; then a ceRNA network with 77 axes related to ferroptosis was established utilizing mutual miRNAs in 2 interaction networks as nodes. Next, a 6-ferroptosis-lncRNA signature including PVT1, CYTOR, MIAT, SNHG17, LINC00265, and LINC00894 was identified in the training set. Kaplan-Meier analysis, PCA, t-SNE analysis, risk score curve, and receiver operating characteristic (ROC) curve were performed to confirm the validity of the signature in the training set and verified in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) analysis showed that the signature was related to immune cell infiltration.
Conclusions: Our research underlines the role of the 6-ferroptosis-lncRNA signature as a predictor of prognosis and a therapeutic alternative for ccRCC.
期刊介绍：
Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly.
Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff.
Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj.
Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker.
The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition.
In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus.
Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.
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