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      A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma


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          Clear cell renal cell carcinoma (ccRCC) is a urinary disease with high incidence. The high incidence of metastasis is the leading cause of death in patients with ccRCC. This study was aimed to identify the gene signatures during the metastasis of ccRCC.


          Two datasets, including one gene expression profile dataset and one microRNA (miRNA) expression profile dataset, were downloaded from Gene Expression Omnibus (GEO) database. The integrated bioinformatics analysis was performed using the (limma) R package, miRWalk, DAVID, STRING, Kaplan-Meier plotter databases. Quantitative real-time polymerase chain reaction (qPCR) was conducted to validate the expression of differentially expressed genes (DEGs) and DE-miRNAs.


          In total, 84 DEGs (68 up-regulated and 16 down-regulated) and 41 DE-miRNAs (24 up-regulated and 17 down-regulated) were screened from GSE22541 and GSE37989 datasets, respectively. Furthermore, 11 hub genes and 3 key miRNAs were identified from the PPI network, including FBLN1, THBS2, SCGB1A1, NKX2-1, COL11A1, DCN, LUM, COL1A1, COL6A3, SFTPC, SFTPB, miR-328, miR-502, and miR-504. The qPCR data showed that most of the selected genes and miRNAs were consistent with that in our integrated analysis. A novel mRNA-miRNA network, SFTPB-miR-328-miR-502-miR-504-NKX2-1 was found in metastatic ccRCC after the combination of data from expression, survival analysis, and experiment validation.


          In conclusion, key candidate genes and miRNAs were identified and a novel mRNA-miRNA network was constructed in ccRCC metastasis using integrated bioinformatics analysis and qPCR validation, which might be utilized as diagnostic biomarkers and molecular targets of metastatic ccRCC.

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          Most cited references51

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          Cancer statistics, 2018

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
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            NCBI GEO: archive for functional genomics data sets—update

            The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.
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              The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.

              Currently, a lack of consensus exists on how best to perform and interpret quantitative real-time PCR (qPCR) experiments. The problem is exacerbated by a lack of sufficient experimental detail in many publications, which impedes a reader's ability to evaluate critically the quality of the results presented or to repeat the experiments. The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines target the reliability of results to help ensure the integrity of the scientific literature, promote consistency between laboratories, and increase experimental transparency. MIQE is a set of guidelines that describe the minimum information necessary for evaluating qPCR experiments. Included is a checklist to accompany the initial submission of a manuscript to the publisher. By providing all relevant experimental conditions and assay characteristics, reviewers can assess the validity of the protocols used. Full disclosure of all reagents, sequences, and analysis methods is necessary to enable other investigators to reproduce results. MIQE details should be published either in abbreviated form or as an online supplement. Following these guidelines will encourage better experimental practice, allowing more reliable and unequivocal interpretation of qPCR results.

                Author and article information

                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                19 January 2021
                : 10
                : 593601
                [1] 1Department of Pathology, The Second Affiliated Hospital of Soochow University , Suzhou, China
                [2] 2Department of Pathology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine , Suzhou, China
                [3] 3Department of Pathology, The People’s hospital of Hainan Tibetan Autonomous Prefecture , Qinghai, China
                [4] 4Department of Pathology, Wuzhong People’s Hospital of Suzhou , Suzhou, China
                Author notes

                Edited by: Xiangqian Guo, Henan University, China

                Reviewed by: Edmund Ui-Hang Sim, Universiti Malaysia Sarawak, Malaysia; Roopa Biswas, Uniformed Services University of the Health Sciences, United States

                *Correspondence: Yongsheng Zhang, shengyongzh@ 123456126.com ; Juan Wang, wxjyrmyy@ 123456163.com

                This article was submitted to Cancer Genetics, a section of the journal Frontiers in Oncology

                †ORCID:Yongsheng Zhang, orcid.org/0000-0002-1857-258X

                ‡These authors have contributed equally to this work

                Copyright © 2021 Yang, Miao, Bai, Tu, Shen, Niu, Xia, Wang and Zhang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 11 August 2020
                : 30 November 2020
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 51, Pages: 11, Words: 4108
                Original Research

                Oncology & Radiotherapy
                clear cell renal cell carcinoma,cancer metastasis,bioinformatics analysis,hub genes,mirnas


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