home icon user icon
Welcome to International Network for Natural Sciences | INNS Pub.
Home My Account
Submit Manuscript
double_slash
breadcumb_bg

Transcriptome analysis reveals PER2 and CRY2 as biomarkers in bladder cancer and circadian rhythm pathways

Paper Details

Research Paper 03/10/2024
Views (29) Download (8)
current_issue_feature_image
publication_file

Transcriptome analysis reveals PER2 and CRY2 as biomarkers in bladder cancer and circadian rhythm pathways

Ehtesham Ahmed Shariff, Amjad Khan, Zafrul Hasan, Ahmed Azharuddin, Rabeena Tabassum
Int. J. Biosci.25( 4), 25-37, October 2024.
Certificate: IJB 2024 [Generate Certificate]
Key: Bladder cancerDifferentially expressed genesGene enrichmentGene ontologyRNA-SeqTranscriptomic profile

Abstract

Bladder cancer RNA-Seq data analysis highlighted significant insights into the molecular mechanisms and biological processes underlying tumorigenesis. Utilizing R packages such as edgeR, limma, and DESeq2, we preprocessed and normalized the data to identify differentially expressed genes (DEGs). Unsupervised learning methods, including PCA, facilitated the classification of these DEGs, revealing critical pathways associated with DNA replication, DNA repair, and cell cycle control. Gene ontology enrichment analysis further delineated the affected biological processes, cellular components, and molecular functions. Notably, our findings identified potential biomarkers, particularly the genes PER2 and CRY2, which are integral to the circadian rhythm pathway. Additionally, we observed that protein complexes CLOCK/BMAL1, CLOCK/BMAL2, and BMAL1/NPAS2 regulate the expression of several clock genes via E-boxes. The study also constructed a differential gene network in bladder cancer, providing insights into the regulatory functions of key genes involved in tumor progression. These findings not only enhance our understanding of bladder cancer biology but also pave the way for potential therapeutic targets and biomarkers.

VIEWS 28
Cover PDF

Abd Elhafeez S, D’Arrigo G, Leonardis D, Fusaro M, Tripepi G, Roumeliotis S. 2021. Methods to analyze time-to-event data: The Cox regression analysis. Oxidative Medicine and Cellular Longevity, 2021. https://doi.org/10.1155/2021/1302811.

Biswas PK, Kwak Y, Kim A, Seok J, Kwak HJ, Lee M, Dayem AA, Song K, Park JY, Park KS, Shin HJ, Cho SG. 2022. TTYH3 modulates bladder cancer proliferation and metastasis via FGFR1/H-Ras/A-Raf/MEK/ERK pathway. International Journal of Molecular Sciences 23(18). https://doi.org/10.3390/ijms231810496.

Bošković M, Roje B, Chung FFL, Gelemanović A, Cahais V, Cuenin C, Khoueiry R, Vilović K, Herceg Z, Terzić J. 2022. DNA methylome changes of muscle- and neuronal-related processes precede bladder cancer invasiveness. Cancers 14(3). https://doi.org/10.3390/cancers14030487.

Champion M, Chiquet J, Neuvial P, Elati M, Radvanyi F, Birmelfie E. 2020. Identification of deregulated transcription factors involved in specific bladder cancer subtypes. EPiC Series in Computing 70, 1–10. https://doi.org/10.29007/v7qj.

Chan AB, Lamia KA. 2020. Cancer, hear my battle CRY. Journal of Pineal Research 69(1). https://doi.org/10.1111/jpi.12658.

Chen C, Liu X, Jiang J, Li S, Wang G, Ju L, Wang F, Liu T, Li S. 2020. Matrix metalloproteinase 11 is a potential biomarker in bladder cancer diagnosis and prognosis. OncoTargets and Therapy 13, 9059–9069. https://doi.org/10.2147/OTT.S243452.

Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, Clark NR, Ma’ayan A. 2013. Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 14(1), 1–14. https://doi.org/10.1186/1471-2105-14-128.

Chen X, Li Y, Paiboonrungruang C, Li Y, Peters H, Kist R, Xiong Z. 2022. PAX9 in cancer development. International Journal of Molecular Sciences 23(10). https://doi.org/10.3390/ijms23105589.

Cieślik M, Chinnaiyan AM. 2018. Cancer transcriptome profiling at the juncture of clinical translation. Nature Reviews Genetics 19(2), 93–109. https://doi.org/10.1038/nrg.2017.96.

Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, Ceccarelli M, Bontempi G, Noushmehr H. 2016. TCGAbiolinks: An R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Research 44(8), e71. https://doi.org/10.1093/nar/gkv1507.

Dangle P, Zaharieva B, Jia H, Pohar K. 2009. Ras-MAPK pathway as a therapeutic target in cancer: Emphasis on bladder cancer. Recent Patents on Anti-Cancer Drug Discovery 4(2), 125–136. https://doi.org/10.2174/157489209788452812.

DeGeorge KC, Holt HR, Hodges SC. 2017. Bladder cancer: Diagnosis and treatment. American Family Physician 96(8), 507–514.

Dobruch J, Oszczudłowski M. 2021. Bladder cancer: Current challenges and future directions. Medicina (Lithuania) 57(8). https://doi.org/10.3390/medicina57080749.

Dyck L, Mills KHG. 2017. Immune checkpoints and their inhibition in cancer and infectious diseases. European Journal of Immunology 47(5), 765–779. https://doi.org/10.1002/eji.201646875.

Fekry B, Eckel-Mahan K. 2022. The circadian clock and cancer: Links between circadian disruption and disease pathology. Journal of Biochemistry 171(5), 477–486. https://doi.org/10.1093/jb/mvac017.

Franzén O, Gan LM, Björkegren JLM. 2019. PanglaoDB: A web server for exploration of mouse and human single-cell RNA sequencing data. Database 2019(1). https://doi.org/10.1093/database/baz046.

Friedman J, Hastie T, Tibshirani R, Narasimhan B, Tay K, Simon N, Qian JY. 2023. glmnet: Lasso and elastic-net regularized generalized linear models. Astrophysics Source Code Library. Record Ascl:2308.011. https://ui.adsabs.harvard.edu/abs/2023ascl.soft08011F.

Garg M, Maurya N. 2019. WNT/β-catenin signaling in urothelial carcinoma of the bladder. World Journal of Nephrology 8(5), 83–94. https://doi.org/10.5527/wjn.v8.i5.83.

Ghojogh B, Crowley M, Karray F, Ghodsi A. 2023. Uniform manifold approximation and projection (UMAP). In Elements of Dimensionality Reduction and Manifold Learning, 479–497. https://doi.org/10.1007/978-3-031-10602-6_17.

Gislefoss RE, Stenehjem JS, Hektoen HH, Andreassen BK, Langseth H, Axcrona K, Weiderpass E, Mondul A, Robsahm TE. 2018. Vitamin D, obesity and leptin in relation to bladder cancer incidence and survival: Prospective protocol study. BMJ Open 8(3). https://doi.org/10.1136/bmjopen-2017-019309.

Gómez-Rubio V. 2017. ggplot2: Elegant graphics for data analysis. Journal of Statistical Software 77(3), 1–3. https://doi.org/10.18637/jss.v077.b02.

Green AK, Milowsky MI. 2016. Genomic profiling of advanced bladder cancer to guide the use of targeted therapeutics. Cancer 122(5), 676–677. https://doi.org/10.1002/cncr.29825.

Hwang B, Lee JH, Bang D. 2018. Single-cell RNA sequencing technologies and bioinformatics pipelines. Experimental and Molecular Medicine 50(8). https://doi.org/10.1038/s12276-018-0071-8.

Ihaka R, Gentleman R. 1996. R: A language for data analysis and graphics. Journal of Computational and Graphical Statistics 5(3), 299–314. https://doi.org/10.1080/10618600.1996.10474713.

Kanehisa M, Goto S. 2000. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research 28(1), 27–30. https://doi.org/10.1093/nar/28.1.27.

Law CW, Chen Y, Shi W, Smyth GK. 2014. Voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biology 15(2). https://doi.org/10.1186/gb-2014-15-2-r29.

Li D, Wu X, Fan X, Cheng C, Li D, Zhang W. 2022. Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer. Annals of Translational Medicine 10(22), 1232–1232. https://doi.org/10.21037/atm-22-5294.

Li X, Liu H, Lv C, Du J, Lian F, Zhang S, Wang Z, Zeng Y. 2022. Gypenoside-induced apoptosis via the PI3K/AKT/mTOR signaling pathway in bladder cancer. BioMed Research International 2022. https://doi.org/10.1155/2022/9304552.

Lin YC, Chen MC, Hsieh TH, Liou JP, Chen CH. 2020. CK1δ as a potential therapeutic target to treat bladder cancer. Aging 12(7), 5764–5780. https://doi.org/10.18632/aging.102966.

Love MI, Huber W, Anders S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology 15(12). https://doi.org/10.1186/s13059-014-0550-8.

Maćkiewicz A, Ratajczak W. 1993. Principal components analysis (PCA). Computers and Geosciences 19(3), 303–342. https://doi.org/10.1016/0098-3004(93)90090-R.

Maeda S, Tomiyasu H, Tsuboi M, Inoue A, Ishihara G, Uchikai T, Chambers JK, Uchida K, Yonezawa T, Matsuki N. 2018. Comprehensive gene expression analysis of canine invasive urothelial bladder carcinoma by RNA-Seq. BMC Cancer 18(1). https://doi.org/10.1186/s12885-018-4409-3.

Martens M, Ammar A, Riutta A, Waagmeester A, Slenter DN, Hanspers K, Miller RA, Digles D, Lopes EN, Ehrhart F, Dupuis LJ, Winckers LA, Coort SL, Willighagen EL, Evelo CT, Pico AR, Kutmon M. 2021. WikiPathways: Connecting communities. Nucleic Acids Research 49(D1), D613–D621. https://doi.org/10.1093/nar/gkaa1024.

Mazzoccoli G, Piepoli A, Carella M, Panza A, Pazienza V, Benegiamo G, Palumbo O, Ranieri E. 2012. Altered expression of the clock gene machinery in kidney cancer patients. Biomedicine and Pharmacotherapy 66(3), 175–179. https://doi.org/10.1016/j.biopha.2011.11.007.

Morgan M, Obenchain V, Hester J, Pagès H. 2021. SummarizedExperiment: Summarized Experiment container. In R package version 1.12.0. https://doi.org/10.18129/B9.bioc.SummarizedExperiment.

Neuwirth E. 2014. RColorBrewer: ColorBrewer palettes. R Package Version 1.1-2. https://cran.r-project.org/web/packages/RColorBrewer/index.html.

Okbah AA, Al-Ankoshy AAM, Al-Shamahy HA. 2022. Bladder cancer: Differentiation of types, age, sex distribution, and associated variants with gradation. Universal Journal of Pharmaceutical Research. https://doi.org/10.22270/ujpr.v6i6.701.

Pramod S, Safriadi F, Hernowo B, Dwiyana R, Batista B. 2020. Smoking history, smoking intensity, and type of cigarette as risk factors of bladder cancer: A literature review. Urological Science 31(4), 147–155. https://doi.org/10.4103/UROS.UROS_6_20.

Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. 2015. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research 43(7), e47. https://doi.org/10.1093/nar/gkv007.

Robinson MD, McCarthy DJ, Smyth GK. 2009. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1), 139–140. https://doi.org/10.1093/bioinformatics/btp616.

Robinson MD, Oshlack A. 2010. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biology 11(3). https://doi.org/10.1186/gb-2010-11-3-r25.

Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. 2020. Epidemiology of bladder cancer. Medical Sciences 8(1). https://doi.org/10.3390/medsci8010015.

Sanguedolce F, Zanelli M, Palicelli A, Ascani S, Zizzo M, Cocco G, Björnebo L, Lantz A, Falagario UG, Cormio L, Carrieri G. 2022. Are we ready to implement molecular subtyping of bladder cancer in clinical practice? Part 1: General issues and marker expression. International Journal of Molecular Sciences 23(14). https://doi.org/10.3390/ijms23147819.

Sato A, Asano T, Okubo K, Isono M, Asano T. 2017. Ritonavir and ixazomib kill bladder cancer cells by causing ubiquitinated protein accumulation. Cancer Science 108(6), 1194–1202. https://doi.org/10.1111/cas.13242.

Schwarzer G. 2007. R Core Team R: A language and environment for statistical computing. R News 40–45. http://www.r-project.org/.

Su S, Law CW, Ah-Cann C, Asselin-Labat ML, Blewitt ME, Ritchie ME. 2017. Glimma: Interactive graphics for gene expression analysis. Bioinformatics 33(13), 2050–2052. https://doi.org/10.1093/bioinformatics/btx094.

Therneau TM. 2023. A package for survival analysis in R. URL: https://cran.r-project.org/package=survival. R Package Version 2.38. https://github.com/therneau/survival.

Vlachostergios PJ, Faltas BM. 2019. The molecular limitations of biomarker research in bladder cancer. World Journal of Urology 37(5), 837–848. https://doi.org/10.1007/s00345-018-2462-9.

Warnes GR, Bolker B, Bonebakker L, Gentleman R, Liaw WHA, Lumley T, Maechler M, Magnusson A, Moeller S, Schwartz M, Venables B. 2019. gplots: Various R programming tools for plotting data. R package version 3.0.1.1. http://CRAN.R-Project.Org/Package=gplots. https://doi.org/10.32614/CRAN.package.gplots.

Wilke CO. 2019. cowplot: Streamlined plot theme and plot annotations for “ggplot2.” R Package Version 1.0.0, 1–44. https://cran.r-project.org/package=cowplot.

Yang J, Song H, Chen L, Cao K, Zhang Y, Li Y, Hao X. 2019. Integrated analysis of microfibrillar-associated proteins reveals MFAP4 as a novel biomarker in human cancers. Epigenomics 11(1), 5–21. https://doi.org/10.2217/epi-2018-0080.

Zhang X, Zhang Y. 2015. Bladder cancer and genetic mutations. Cell Biochemistry and Biophysics 73(1), 65–69. https://doi.org/10.1007/s12013-015-0574-z.

Zhao F, Ge YZ, Zhou LH, Xu LW, Xu Z, Ping WW, Wang M, Zhou CC, Wu R, Jia RP. 2017. Identification of hub miRNA biomarkers for bladder cancer by weighted gene coexpression network analysis. OncoTargets and Therapy 10, 5551–5559. https://doi.org/10.2147/OTT.S146479.

Zhu J, Pan X, Zhang Z, Gao J, Zhang L, Chen J. 2012. Downregulation of integrin-linked kinase inhibits epithelial-to-mesenchymal transition and metastasis in bladder cancer cells. Cellular Signalling 24(6), 1323–1332. https://doi.org/10.1016/j.cellsig.2012.02.013.

Submit Manuscript