Model Construction and Identification of Genome Instability-Associated lncRNA Signature Markers in Bladder Cancer
Abstract
Background: Studies have shown that long non-coding RNA (LncRNA) plays a critical role in maintaining genomic instability. As a new tumor marker, the correlation between lncRNA and genomic instability is still worth exploring in bladder cancer.
Methods: Therefore, combined with the lncRNA expression profile and somatic mutation profile of bladder cancer, we established a computing framework of lncRNA related to genomic instability and identified 58 new lncRNA related to genomic instability. Next, we identified a lncRNA signature (GILncSig), based on these 58 new genes, which divided patients into high-risk and low-risk groups. The clinical prognosis was significantly different and was further verified in an independent cohort of patients.
Results: We confirmed that GILncSig is related to the genomic mutation rate of bladder cancer, suggesting that GILncSig can be used as an indicator of genomic instability. The results show that GILncSig has prognostic value independent of age, sex, grade, and stage, and plays an important role in evaluating clinical prognosis. To sum up, this study provides an important research basis and methods for further exploring the role of lncRNA in genomic instability of bladder cancer, and provides a theoretical basis for the identification of bladder cancer biomarkers related to genomic instability.
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John, B.A. and N. Said, Insights from animal models of bladder cancer: recent advances, challenges, and opportunities. Oncotarget, 2017. 8(34): p. 57766-57781.
Jazzar, U., et al., Impact of psychiatric illness on decreased survival in elderly patients with bladder cancer in the United States. Cancer, 2018. 124(15): p. 3127-3135.
Şanlı, Ö. and Y. Lotan, Alternative therapies in patients with non-muscle invasive bladder cancer. Turk J Urol, 2017. 43(4): p. 414-424.
Snell, K.I.E., et al., Exploring the roles of urinary HAI-1, EpCAM & EGFR in bladder cancer prognosis & risk stratification. Oncotarget, 2018. 9(38): p. 25244-25253.
Grayson, M., Bladder cancer. Nature, 2017. 551(7679): p. S33.
Andor, N., C.C. Maley, and H.P. Ji, Genomic Instability in Cancer: Teetering on the Limit of Tolerance. Cancer Res, 2017. 77(9): p. 2179-2185.
Duijf, P.H.G., et al., Mechanisms of Genomic Instability in Breast Cancer. Trends Mol Med, 2019. 25(7): p. 595-611.
Ben-David, U., R. Beroukhim, and T.R. Golub, Genomic evolution of cancer models: perils and opportunities. Nat Rev Cancer, 2019. 19(2): p. 97-109.
Tam, A.S., et al., Selective defects in gene expression control genome instability in yeast splicing mutants. Mol Biol Cell, 2019. 30(2): p. 191-200.
Boysen, G., et al., SPOP mutation leads to genomic instability in prostate cancer. Elife, 2015. 4.
Biermann, J., et al., A 17-marker panel for global genomic instability in breast cancer. Genomics, 2020. 112(2): p. 1151-1161.
Choudhari, R., et al., Long noncoding RNAs in cancer: From discovery to therapeutic targets. Adv Clin Chem, 2020. 95: p. 105-147.
Kopp, F. and J.T. Mendell, Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell, 2018. 172(3): p. 393-407.
St Laurent, G., C. Wahlestedt, and P. Kapranov, The Landscape of long noncoding RNA classification. Trends Genet, 2015. 31(5): p. 239-51.
Cao, H.L., et al., lncRNA-RMRP promotes proliferation, migration and invasion of bladder cancer via miR-206. Eur Rev Med Pharmacol Sci, 2019. 23(3): p. 1012-1021.
Sun, W., N.M. Shen, and S.L. Fu, Involvement of lncRNA-mediated signaling pathway in the development of cervical cancer. Eur Rev Med Pharmacol Sci, 2019. 23(9): p. 3672-3687.
Wang, J., et al., LncRNA HOXA-AS2 and its molecular mechanisms in human cancer. Clin Chim Acta, 2018. 485: p. 229-233.
Zhao, W., et al., LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer. Cancer Med, 2018. 7(3): p. 842-855.
Liu, H., Linking lncRNA to genomic stability. Sci China Life Sci, 2016. 59(3): p. 328-9.
Tracy, K.M., et al., Mitotically-Associated lncRNA (MANCR) Affects Genomic Stability and Cell Division in Aggressive Breast Cancer. Mol Cancer Res, 2018. 16(4): p. 587-598.
Zhang, C. and G. Peng, Non-coding RNAs: an emerging player in DNA damage response. Mutation research. Reviews in mutation research, 2015. 763: p. 202-211.
Yu, G., et al., DOSE: An R/Bioconductor package for disease ontology semantic and enrichment analysis. Bioinformatics, 2015. 31(4): p. 608-9.
Cao, R., et al., Immune-related long non-coding RNA signature identified prognosis and immunotherapeutic efficiency in bladder cancer (BLCA). Cancer cell international, 2020. 20: p. 276.
Lian, P., et al., An eight-long non-coding RNA signature as a candidate prognostic biomarker for bladder cancer. Aging, 2019. 11(17): p. 6930-6940.
Zhang, X., et al., A prognostic index based on a fourteen long non-coding RNA signature to predict the recurrence-free survival for muscle-invasive bladder cancer patients. BMC medical informatics and decision making, 2020. 20(Suppl 3): p. 136.
Ou, Z., et al., Detection of bladder cancer using urinary cell-free DNA and cellular DNA. Clinical and translational medicine, 2020. 9(1): p. 4.
Ciccarese, C., et al., Tp53 and its potential therapeutic role as a target in bladder cancer. Expert Opin Ther Targets, 2017. 21(4): p. 401-414.
Almeida, T.C., et al., Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status. Environmental and molecular mutagenesis, 2019. 60(8): p. 740-751.
Lyu, Q., et al., Alterations in TP53 Are a Potential Biomarker of Bladder Cancer Patients Who Benefit from Immune Checkpoint Inhibition. Cancer control: journal of the Moffitt Cancer Center, 2020. 27(1): p. 1073274820976665.
Patel, V.G., W.K. Oh, and M.D. Galsky, Treatment of muscle-invasive and advanced bladder cancer in 2020. CA: a cancer journal for clinicians, 2020. 70(5): p. 404-423.
Guo, C.C. and B. Czerniak, Bladder Cancer in the Genomic Era. Arch Pathol Lab Med, 2019. 143(6): p. 695-704.
Hayashi, T., et al., Mutational Landscape and Environmental Effects in Bladder Cancer. Int J Mol Sci, 2020. 21(17).
Grossman, H.B., et al., Innovation in Bladder Cancer Immunotherapy. J Immunother, 2016. 39(8): p. 291-7.
Humphrey, P.A., et al., The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. European urology, 2016. 70(1): p. 106-119.
Wang, G. and J.K. McKenney, Urinary Bladder Pathology: World Health Organization Classification and American Joint Committee on Cancer Staging Update. Archives of pathology & laboratory medicine, 2019. 143(5): p. 571-577.
Alifrangis, C., et al., Molecular and histopathology directed therapy for advanced bladder cancer. Nature reviews. Urology, 2019. 16(8): p. 465-483.
Tan, T.Z., et al., Molecular Subtypes of Urothelial Bladder Cancer: Results from a Meta-cohort Analysis of 2411 Tumors. European urology, 2019. 75(3): p. 423-432.
Minoli, M., et al., Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications. International journal of molecular sciences, 2020. 21(16).
Matulay, J.T., V.M. Narayan, and A.M. Kamat, Clinical and Genomic Considerations for Variant Histology in Bladder Cancer. Current oncology reports, 2019. 21(3): p. 23.
Bartek, J., J. Bartkova, and J. Lukas, DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene, 2007. 26(56): p. 7773-7779.
Bakhoum, S.F., et al., Chromosomal instability drives metastasis through a cytosolic DNA response. Nature, 2018. 553(7689): p. 467-472.
Petropoulos, M., et al., Replication Licensing Aberrations, Replication Stress, and Genomic Instability. Trends in biochemical sciences, 2019. 44(9): p. 752-764.
Vacher, S., et al., Genomic Instability Signature of Palindromic Non-Coding Somatic Mutations in Bladder Cancer. Cancers (Basel), 2020. 12(10).
Yang, Y., et al., Complete response to anti-PD-L1 antibody in a metastatic bladder cancer associated with novel MSH4 mutation and microsatellite instability. Journal for immunotherapy of cancer, 2020. 8(1).
Biermann, J., et al., Radiation-induced genomic instability in breast carcinomas of the Swedish hemangioma cohort. Genes, chromosomes & cancer, 2019. 58(9): p. 627-635.
Ferguson, L.R., et al., Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Seminars in cancer biology, 2015. 35 Suppl.
Hypoxic Tumors Share Genomic Instability. Cancer discovery, 2019. 9(3): p. 314.
Lee, J.-H., et al., MicroRNA-22 Suppresses DNA Repair and Promotes Genomic Instability through Targeting of MDC1. Cancer research, 2015. 75(7): p. 1298-1310.
Bhan, A., M. Soleimani, and S.S. Mandal, Long Noncoding RNA and Cancer: A New Paradigm. Cancer research, 2017. 77(15): p. 3965-3981.
Rathinasamy, B. and B.K. Velmurugan, Role of lncRNAs in the cancer development and progression and their regulation by various phytochemicals. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018. 102: p. 242-248.
Dastmalchi, N., R. Safaralizadeh, and M.M. Nargesi, LncRNAs: Potential Novel Prognostic and Diagnostic Biomarkers in Colorectal Cancer. Current medicinal chemistry, 2020. 27(30): p. 5067-5077.
Amodio, N., et al., MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches. Journal of hematology & oncology, 2018. 11(1): p. 63.
Idogawa, M., et al., Long non-coding RNA NEAT1 is a transcriptional target of p53 and modulates p53-induced transactivation and tumor-suppressor function. International journal of cancer, 2017. 140(12): p. 2785-2791.
Ovejero, S., A. Bueno, and M.P. Sacristán, Working on Genomic Stability: From the S-Phase to Mitosis. Genes (Basel), 2020. 11(2).
Petsalaki, E. and G. Zachos, DNA damage response proteins regulating mitotic cell division: double agents preserving genome stability. The FEBS journal, 2020. 287(9): p. 1700-1721.
Duchartre, Y., Y.M. Kim, and M. Kahn, The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol, 2016. 99: p. 141-9.
Gu, J., et al., A genome-wide association study identifies a locus on chromosome 14q21 as a predictor of leukocyte telomere length and as a marker of susceptibility for bladder cancer. Cancer prevention research (Philadelphia, Pa.), 2011. 4(4): p. 514-521.
Gago-Dominguez, M., et al., Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study. Carcinogenesis, 2011. 32(2): p. 197-202.
DOI: http://dx.doi.org/10.18686/jn.v10i1.191
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