Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
February-2021 Volume 21 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2021 Volume 21 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.xlsx
    • Supplementary_Data3.xlsx
    • Supplementary_Data4.xlsx
Article Open Access

Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma

  • Authors:
    • Jiting Qiu
    • Chunhui Wang
    • Hongkang Hu
    • Sarah Chen
    • Xuehua Ding
    • Yu Cai
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201803, P.R. China, Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27514, USA
    Copyright: © Qiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 138
    |
    Published online on: December 20, 2020
       https://doi.org/10.3892/ol.2020.12399
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Glioblastoma (GBM) is the most aggressive malignant brain tumour, with high morbidity and mortality rates. Currently, there is a lack of systematic and comprehensive analysis on the prognostic significance of alternative splicing (AS) profiling for GBM. The GBM data, including RNA‑sequencing, corresponding clinical information and the expression levels of splicing factor genes, were downloaded from The Cancer Genome Atlas and the SpliceAid2 database. The prognostic models were assessed by the least absolute shrinkage and selection operator Cox regression analysis. The correlation network between survival‑associated AS events and splicing factors was plotted. Prognostic models were built for every AS event type and performed well for risk stratification in patients with GBM. The final prognostic signature served as an independent prognostic factor [hazard ratio (HR), 4.61; 95% confidence interval (CI), 2.97‑7.16; P=9.66x10‑12] for several clinical parameters, including age, sex, isocitrate dehydrogenase mutation, O6‑methylguanine‑DNA methyltransferase promoter methylation and risk score. The HR for risk score with GBM was 1.0063 (95% CI, 1.0024‑1.0103). The splicing regulatory network indicated that heat shock protein b‑1, protein arginine N‑methyltransferase 5, protein FAM50B and endoplasmic reticulum chaperone BiP genes were independent prognostic factors for GBM. The results of the present study support the ongoing effort in developing novel genomic models and providing potentially more effective treatment options for patients with GBM.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol. 15 (Suppl 2):ii1–ii56. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Binabaj MM, Bahrami A, ShahidSales S, Joodi M, Joudi Mashhad M, Hassanian SM, Anvari K and Avan A: The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials. J Cell Physiol. 233:378–386. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Zhao W, Li J, Chen MM, Luo Y, Ju Z, Nesser NK, Johnson-Camacho K, Boniface CT, Lawrence Y, Pande NT, et al: Large-scale characterization of drug responses of clinically relevant proteins in cancer cell lines. Cancer Cell. Oct 2–2020.doi: 10.1016/j.ccell.2020.10.008 (Online ahead of print). View Article : Google Scholar

5 

Singh B and Eyras E: The role of alternative splicing in cancer. Transcription. 8:91–98. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Liu Y, Shi N, Regev A, He S and Hemann MT: Integrated regulatory models for inference of subtype-specific susceptibilities in glioblastoma. Mol Syst Biol. 16:e95062020. View Article : Google Scholar : PubMed/NCBI

7 

Du J, Yan X, Mi S, Li Y, Ji H, Hou K, Ma S, Ba Y, Zhou P, Chen L, et al: Identification of prognostic model and biomarkers for cancer stem cell characteristics in glioblastoma by network analysis of multi-omics data and stemness indices. Front Cell Dev Biol. 8:5589612020. View Article : Google Scholar : PubMed/NCBI

8 

Bao ZS, Li MY, Wang JY, Zhang CB, Wang HJ, Yan W, Liu YW, Zhang W, Chen L and Jiang T: Prognostic value of a nine-gene signature in glioma patients based on mRNA expression profiling. CNS Neurosci Ther. 20:112–118. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Yin W, Tang G, Zhou Q, Cao Y, Li H, Fu X, Wu Z and Jiang X: Expression profile analysis identifies a novel five-gene signature to improve prognosis prediction of glioblastoma. Front Genet. 10:4192019. View Article : Google Scholar : PubMed/NCBI

10 

Carpenter S, Ricci EP, Mercier BC, Moore MJ and Fitzgerald KA: Post-transcriptional regulation of gene expression in innate immunity. Nat Rev Immunol. 14:361–376. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Nilsen TW and Graveley BR: Expansion of the eukaryotic proteome by alternative splicing. Nature. 463:457–463. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Antonopoulou E and Ladomery M: Targeting splicing in prostate cancer. Int J Mol Sci. 19:12872018. View Article : Google Scholar

13 

Kim HK, Pham MHC, Ko KS, Rhee BD and Han J: Alternative splicing isoforms in health and disease. Pflugers Arch. 470:995–1016. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Brosseau JP, Lucier JF, Nwilati H, Thibault P, Garneau D, Gendron D, Durand M, Couture S, Lapointe E, Prinos P, et al: Tumor microenvironment-associated modifications of alternative splicing. RNA. 20:189–201. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Dvinge H, Kim E, Abdel-Wahab O and Bradley RK: RNA splicing factors as oncoproteins and tumour suppressors. Nat Rev Cancer. 16:413–430. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Lee Y and Rio DC: Mechanisms and regulation of alternative Pre-mRNA splicing. Annu Rev Biochem. 84:291–323. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Martinez-Montiel N, Rosas-Murrieta NH, Anaya Ruiz M, Monjaraz-Guzman E and Martinez-Contreras R: Alternative splicing as a target for cancer treatment. Int J Mol Sci. 19:5452018. View Article : Google Scholar

18 

Suñé-Pou M, Prieto-Sánchez S, Boyero-Corral S, Moreno-Castro C, El Yousfi Y, Suñé-Negre JM, Hernández-Munain C and Suñé C: Targeting splicing in the treatment of human disease. Genes (Basel). 8:872017. View Article : Google Scholar

19 

Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, et al: Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 17:510–522. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Ryan M, Wong WC, Brown R, Akbani R, Su X, Broom B, Melott J and Weinstein J: TCGASpliceSeq a compendium of alternative mRNA splicing in cancer. Nucleic Acids Res. 44:D1018–D1022. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Ryan MC, Cleland J, Kim R, Wong WC and Weinstein JN: SpliceSeq: A resource for analysis and visualization of RNA-Seq data on alternative splicing and its functional impacts. Bioinformatics. 28:2385–2387. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Lex A, Gehlenborg N, Strobelt H, Vuillemot R and Pfister H: UpSet: Visualization of intersecting sets. IEEE Trans Vis Comput Graph. 20:1983–1992. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Wu G, Feng X and Stein L: A human functional protein interaction network and its application to cancer data analysis. Genome Biol. 11:R532010. View Article : Google Scholar : PubMed/NCBI

24 

Tibshirani R: The lasso method for variable selection in the Cox model. Stat Med. 16:385–395. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Heagerty PJ, Lumley T and Pepe MS: Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 56:337–344. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Szopa W, Burley TA, Kramer-Marek G and Kaspera W: Diagnostic and therapeutic biomarkers in glioblastoma: Current status and future perspectives. Bio Res Int. 2017:80135752017.

27 

Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, et al: Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): A randomised controlled phase 2 trial. Lancet Oncol. 15:943–953. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Aldape K, Zadeh G, Mansouri S, Reifenberger G and von Deimling A: Glioblastoma: Pathology, molecular mechanisms and markers. Acta Neuropathol. 129:829–848. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Zeng Y, Zhang P, Wang X, Wang K, Zhou M, Long H, Lin J, Wu Z, Gao L and Song Y: Identification of prognostic signatures. 2020.

30 

Xie ZC, Wu HY, Dang YW and Chen G: Role of alternative splicing signatures in the prognosis of glioblastoma. Cancer Med. 8:7623–7636. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Chen X, Zhao C, Guo B, Zhao Z, Wang H and Fang Z: Systematic profiling of alternative mRNA splicing signature for predicting glioblastoma prognosis. Front Oncol. 9:9282019. View Article : Google Scholar : PubMed/NCBI

32 

Li Y, Ren Z, Peng Y, Li K, Wang X, Huang G, Qi S and Liu Y: Classification of glioma based on prognostic alternative splicing. BMC Med Genomics. 12:1652019. View Article : Google Scholar : PubMed/NCBI

33 

Zhang J and Manley JL: Misregulation of pre-mRNA alternative splicing in cancer. Cancer Discov. 3:1228–1237. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Qi Z, Shen L, Zhou H, Jiang Y, Lan L, Luo L and Yin Z: Phosphorylation of heat shock protein 27 antagonizes TNF-α induced HeLa cell apoptosis via regulating TAK1 ubiquitination and activation of p38 and ERK signaling. Cell Signal. 26:1616–1625. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Banasavadi-Siddegowda YK, Russell L, Frair E, Karkhanis VA, Relation T, Yoo JY, Zhang J, Sif S, Imitola J, Baiocchi R and Kaur B: PRMT5-PTEN molecular pathway regulates senescence and self-renewal of primary glioblastoma neurosphere cells. Oncogene. 36:263–274. 2017. View Article : Google Scholar : PubMed/NCBI

36 

Banasavadi-Siddegowda YK, Welker AM, An M, Yang X, Zhou W, Shi G, Imitola J, Li C, Hsu S, Wang J, et al: PRMT5 as a druggable target for glioblastoma therapy. Neuro Oncol. 20:753–763. 2018. View Article : Google Scholar : PubMed/NCBI

37 

Jia D, Lin W, Tang H, Cheng Y, Xu K, He Y, Geng W and Dai Q: Integrative analysis of DNA methylation and gene expression to identify key epigenetic genes in glioblastoma. Aging (Albany NY). 11:5579–5592. 2019. View Article : Google Scholar : PubMed/NCBI

38 

Cerezo M and Rocchi S: New anti-cancer molecules targeting HSPA5/BIP to induce endoplasmic reticulum stress, autophagy and apoptosis. Autophagy. 13:216–217. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Qiu J, Wang C, Hu H, Chen S, Ding X and Cai Y: Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma. Oncol Lett 21: 138, 2021.
APA
Qiu, J., Wang, C., Hu, H., Chen, S., Ding, X., & Cai, Y. (2021). Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma. Oncology Letters, 21, 138. https://doi.org/10.3892/ol.2020.12399
MLA
Qiu, J., Wang, C., Hu, H., Chen, S., Ding, X., Cai, Y."Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma". Oncology Letters 21.2 (2021): 138.
Chicago
Qiu, J., Wang, C., Hu, H., Chen, S., Ding, X., Cai, Y."Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma". Oncology Letters 21, no. 2 (2021): 138. https://doi.org/10.3892/ol.2020.12399
Copy and paste a formatted citation
x
Spandidos Publications style
Qiu J, Wang C, Hu H, Chen S, Ding X and Cai Y: Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma. Oncol Lett 21: 138, 2021.
APA
Qiu, J., Wang, C., Hu, H., Chen, S., Ding, X., & Cai, Y. (2021). Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma. Oncology Letters, 21, 138. https://doi.org/10.3892/ol.2020.12399
MLA
Qiu, J., Wang, C., Hu, H., Chen, S., Ding, X., Cai, Y."Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma". Oncology Letters 21.2 (2021): 138.
Chicago
Qiu, J., Wang, C., Hu, H., Chen, S., Ding, X., Cai, Y."Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma". Oncology Letters 21, no. 2 (2021): 138. https://doi.org/10.3892/ol.2020.12399
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team