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Establishing a Prognostic Model Based on Three Genomic Instability-related LncRNAs for Clear Cell Renal Cell Cancer

  • Author Footnotes
    † These authors have contributed equally to this work
    Shen Lulu
    Footnotes
    † These authors have contributed equally to this work
    Affiliations
    Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    † These authors have contributed equally to this work
    Hou Hualing
    Footnotes
    † These authors have contributed equally to this work
    Affiliations
    Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Zhang Shan
    Affiliations
    Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Chen Dianxi
    Affiliations
    Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Li Yiqing
    Correspondence
    Address for correspondence: Li Yiqing, Li Qin, MD, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, P.R. China
    Affiliations
    Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for articles by this author
  • Li Qin
    Correspondence
    Address for correspondence: Li Yiqing, Li Qin, MD, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, P.R. China
    Affiliations
    Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Search for articles by this author
  • Author Footnotes
    † These authors have contributed equally to this work
Published:February 23, 2022DOI:https://doi.org/10.1016/j.clgc.2022.02.005

      Abstract

      Background

      Among all types of renal cell cancer (RCC), clear cell renal cell cancer (ccRCC) is the most common and aggressive one. Emerging evidence uncovers that long non-coding RNAs (lncRNAs) are involved in genomic instability, which correlates to the clinical outcomes of patients who suffer from various kinds of cancers.

      Methods

      We gathered expression profiles of transcriptome RNA and clinical information about ccRCC from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database. The lncRNA expression profiles and somatic mutation data were combined to identify genome instability-related lncRNAs (GILncRs) by significance analysis of T test. By means of univariate and multivariate cox regression analyses, 3 GILncRs strongly associated with patient prognosis were screened out to build a genomic instability-related risk score (GIRS) model. We use R-version 4.0.4 to draw Kaplan-Meier plots and ROC curves for survival prediction.

      Results

      The somatic mutation count was higher in genomic unstable group. PBRM1 showed lower expression in genomic unstable group. Three lncRNAs such as LINC00460, AC156455.1, LINC01606 were included in the GIRS model. Patients had poorer prognosis with higher risk score of GIRS model. The somatic mutation count was higher in patients with higher risk score while PBRM1 expression was lower. The GIRS model was independent from other clinical factors. The GIRS model was superior to other 2 published lncRNA signatures in survival prediction.

      Keywords

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      References

        • Capitanio U.
        • Bensalah K.
        • Bex A.
        • et al.
        Epidemiology of renal cell carcinoma.
        Eur Urol. 2019; 75: 74-84https://doi.org/10.1016/j.eururo.2018.08.036
        • O'Rourke C.J.
        • Knabben V.
        • Bolton E.
        • et al.
        Manipulating the epigenome for the treatment of urological malignancies.
        Pharmacol Ther. 2013; 138: 185-196https://doi.org/10.1016/j.pharmthera.2013.01.007
        • Linehan W.M.
        Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics.
        Genome Res. 2012; 22: 2089-2100https://doi.org/10.1101/gr.131110.111
        • Vuong L.
        • Kotecha R.R.
        • Voss M.H.
        • Hakimi A.A.
        Tumor microenvironment dynamics in clear-cell renal cell carcinoma.
        Cancer Discov. 2019; 9: 1349-1357https://doi.org/10.1158/2159-8290.CD-19-0499
        • Rydzanicz M.
        • Wrzesinski T.
        • Bluyssen H.A.
        • Wesoly J.
        Genomics and epigenomics of clear cell renal cell carcinoma: recent developments and potential applications.
        Cancer Lett. 2013; 341: 111-126https://doi.org/10.1016/j.canlet.2013.08.006
        • Song M.
        Recent developments in small molecule therapies for renal cell carcinoma.
        Eur J Med Chem. 2017; 142: 383-392https://doi.org/10.1016/j.ejmech.2017.08.007
        • Sanchez-Gastaldo A.
        • Kempf E.
        • Gonzalez Del Alba A.
        • Duran I.
        Systemic treatment of renal cell cancer: A comprehensive review.
        Cancer Treat Rev. 2017; 60: 77-89https://doi.org/10.1016/j.ctrv.2017.08.010
        • Guo C.
        • Zhao H.
        • Wang Y.
        • et al.
        Prognostic value of the neo-immunoscore in renal cell carcinoma.
        Front Oncol. 2019; 9: 439https://doi.org/10.3389/fonc.2019.00439
        • Negrini S.
        • Gorgoulis V.G.
        • Halazonetis T.D.
        Genomic instability–an evolving hallmark of cancer.
        Nat Rev Mol Cell Biol. 2010; 11: 220-228https://doi.org/10.1038/nrm2858
        • Kalimutho M.
        • Nones K.
        • Srihari S.
        • Duijf P.H.G.
        • Waddell N.
        • Khanna K.K.
        Patterns of genomic instability in breast cancer.
        Trends Pharmacol Sci. 2019; 40: 198-211https://doi.org/10.1016/j.tips.2019.01.005
        • Poole L.A.
        • Cortez D.
        Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability.
        Crit Rev Biochem Mol Biol. 2017; 52: 696-714https://doi.org/10.1080/10409238.2017.1380597
        • Syed A.
        • Tainer J.A.
        The MRE11-RAD50-NBS1 complex conducts the orchestration of damage signaling and outcomes to stress in DNA replication and repair.
        Annu Rev Biochem. 2018; 87: 263-294https://doi.org/10.1146/annurev-biochem-062917-012415
        • Cheetham S.W.
        • Gruhl F.
        • Mattick J.S.
        • Dinger M.E.
        Long noncoding RNAs and the genetics of cancer.
        Br J Cancer. 2013; 108: 2419-2425https://doi.org/10.1038/bjc.2013.233
        • Moghaddas Sani H.
        • Hejazian M.
        • Hosseinian Khatibi S.M.
        • Ardalan M.
        • Zununi Vahed S.
        Long non-coding RNAs: An essential emerging field in kidney pathogenesis.
        Biomed Pharmacother. 2018; 99: 755-765https://doi.org/10.1016/j.biopha.2018.01.122
        • Martens-Uzunova E.S.
        • Bottcher R.
        • Croce C.M.
        • Jenster G.
        • Visakorpi T.
        • Calin G.A.
        Long noncoding RNA in prostate, bladder, and kidney cancer.
        Eur Urol. 2014; 65: 1140-1151https://doi.org/10.1016/j.eururo.2013.12.003
        • Lee S.
        • Kopp F.
        • Chang T.C.
        • et al.
        Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins.
        Cell. 2016; 164: 69-80https://doi.org/10.1016/j.cell.2015.12.017
        • Munschauer M.
        • Nguyen C.T.
        • Sirokman K.
        • et al.
        The NORAD lncRNA assembles a topoisomerase complex critical for genome stability.
        Nature. 2018; 561: 132-136https://doi.org/10.1038/s41586-018-0453-z
        • Hu W.L.
        • Jin L.
        • Xu A.
        • et al.
        GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability.
        Nat Cell Biol. 2018; 20: 492-502https://doi.org/10.1038/s41556-018-0066-7
        • Khanduja J.S.
        • Calvo I.A.
        • Joh R.I.
        • Hill I.T.
        • Motamedi M.
        Nuclear noncoding RNAs and genome stability.
        Mol Cell. 2016; 63: 7-20https://doi.org/10.1016/j.molcel.2016.06.011
        • Khorkova O.
        • Hsiao J.
        • Wahlestedt C.
        Basic biology and therapeutic implications of lncRNA.
        Adv Drug Deliv Rev. 2015; 87: 15-24https://doi.org/10.1016/j.addr.2015.05.012
        • Rothschild G.
        • Basu U.
        Lingering questions about enhancer RNA and enhancer transcription-coupled genomic instability.
        Trends Genet. 2017; 33: 143-154https://doi.org/10.1016/j.tig.2016.12.002
        • Wan G.
        • Liu Y.
        • Han C.
        • Zhang X.
        • Lu X.
        Noncoding RNAs in DNA repair and genome integrity.
        Antioxid Redox Signal. 2014; 20: 655-677https://doi.org/10.1089/ars.2013.5514
        • Ricketts C.J.
        • De Cubas A.A.
        • Fan H.
        • et al.
        The cancer genome atlas comprehensive molecular characterization of renal cell carcinoma.
        Cell Rep. 2018; 23 (e315): 313-326https://doi.org/10.1016/j.celrep.2018.03.075
        • Cai W.
        • Su L.
        • Liao L.
        • et al.
        PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth.
        Nat Commun. 2019; 10: 5800https://doi.org/10.1038/s41467-019-13608-1
        • Espana-Agusti J.
        • Warren A.
        • Chew S.K.
        • Adams D.J.
        • Matakidou A.
        Loss of PBRM1 rescues VHL dependent replication stress to promote renal carcinogenesis.
        Nat Commun. 2017; 8: 2026https://doi.org/10.1038/s41467-017-02245-1
        • Liu H.
        • Ye T.
        • Yang X.
        • et al.
        A panel of four-lncRNA signature as a potential biomarker for predicting survival in clear cell renal cell carcinoma.
        J Cancer. 2020; 11: 4274-4283https://doi.org/10.7150/jca.40421
        • Luo Y.
        • Tan W.
        • Jia W.
        • et al.
        The long non-coding RNA LINC01606 contributes to the metastasis and invasion of human gastric cancer and is associated with Wnt/beta-catenin signaling.
        Int J Biochem Cell Biol. 2018; 103: 125-134https://doi.org/10.1016/j.biocel.2018.08.012
        • Couzin-Frankel J.
        Science communication. backlash greets 'bad luck' cancer study and coverage.
        Science. 2015; 347: 224https://doi.org/10.1126/science.347.6219.224
        • Chen W.
        • Hill H.
        • Christie A.
        • et al.
        Targeting renal cell carcinoma with a HIF-2 antagonist.
        Nature. 2016; 539: 112-117https://doi.org/10.1038/nature19796
        • Courtney K.D.
        • Ma Y.
        • Diaz de Leon A.
        • et al.
        HIF-2 complex dissociation, target inhibition, and acquired resistance with PT2385, a first-in-class HIF-2 inhibitor, in patients with clear cell renal cell Carcinoma.
        Clin Cancer Res. 2020; 26: 793-803https://doi.org/10.1158/1078-0432.CCR-19-1459
        • Miao D.
        • Margolis C.A.
        • Gao W.
        • et al.
        Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma.
        Science. 2018; 359: 801-806https://doi.org/10.1126/science.aan5951