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
September-2018 Volume 16 Issue 3

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
September-2018 Volume 16 Issue 3

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
Article Open Access

Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection

  • Authors:
    • Zhifei Lin
    • Huliang Jia
    • Liang Hong
    • Yahui Zheng
    • Weiqin Shao
    • Xudong Ren
    • Wenwei Zhu
    • Lu Lu
    • Ming Lu
    • Jubo Zhang
    • Jinhong Chen
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Infectious Diseases, Ruian People's Hospital, Wenzhou, Zhejiang 325200, P.R. China, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3665-3673
    |
    Published online on: July 5, 2018
       https://doi.org/10.3892/ol.2018.9083
  • 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

Histone methyltransferases are important determinants of the initiation and progression of hepatocellular carcinoma (HCC) and represent promising therapeutic targets. However, whether the expression profile of multiple histone methyltransferases represents a poorer prognosis is entirely unknown. The aim of the present study was to investigate the association between histone methylation and HCC phenotype, and the prognostic value of combining expression levels of SET domain‑containing protein 8 (SET8) with protein arginine methyltransferase 5 (PRMT5) in patients with HCC following curative resection. The retrospective study included 195 consecutive patients who had undergone hepatectomy for HCC. Immunohistochemical staining for SET8 and PRMT5 was performed on paraffin‑embedded tumor tissue microarrays. Expression was analyzed for correlations with clinicopathological features, marker co‑expression and patients' survival by univariate and multivariate analyses. Positive SET8 expression was noted in 104 patients (53.3%), and was associated with PRMT5 expression (n=106, 54.4%, P<0.05). Immunohistochemical analysis demonstrated that high expression of SET8 and PRMT5 was significantly associated with poor overall survival (OS, P<0.001) and time to recurrence (TTR, P<0.001). Multivariate Cox analysis revealed that SET8 and PRMT5, along with vascular invasion, tumor size and tumor number, were independent prognostic factors for OS and TTR. The combination of SET8 and PRMT5 demonstrated an improved capacity to predict patient mortality and disease recurrence (P=0.002 and P=0.004, respectively), particularly for the prediction of early recurrence (P<0.001). In conclusion, high expression of SET8 combined with PRMT5 was associated with a high rate of recurrence and poor survival in patients with HCC. The independent pattern of histone methylation represents a novel insight into tumor progression and therapeutic targets for HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Liu M, Jiang L and Guan XY: The genetic and epigenetic alterations in human hepatocellular carcinoma: A recent update. Protein Cell. 5:673–691. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Ma L, Chua MS, Andrisani O and So S: Epigenetics in hepatocellular carcinoma: An update and future therapy perspectives. World J Gastroenterol. 20:333–345. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Herath NI, Leggett BA and MacDonald GA: Review of genetic and epigenetic alterations in hepatocarcinogenesis. J Gastroenterol Hepatol. 21:15–21. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Wahid B, Ali A, Rafique S and Idrees M: New insights into the epigenetics of hepatocellular carcinoma. Biomed Res Int. 2017:16095752017. View Article : Google Scholar : PubMed/NCBI

5 

Pogribny IP and Rusyn I: Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma. Cancer Lett. 342:223–230. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Fang J, Feng Q, Ketel CS, Wang H, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Simon JA and Zhang Y: Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol. 12:1086–1099. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Xiao B, Jing C, Kelly G, Walker PA, Muskett FW, Frenkiel TA, Martin SR, Sarma K, Reinberg D, Gamblin SJ and Wilson JR: Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev. 19:1444–1454. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Nishioka K, Rice JC, Sarma K, Erdjument-Bromage H, Werner J, Wang Y, Chuikov S, Valenzuela P, Tempst P, Steward R, et al: PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell. 9:1201–1213. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Houston SI, McManus KJ, Adams MM, Sims JK, Carpenter PB, Hendzel MJ and Rice JC: Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry and genomic stability. J Biol Chem. 283:19478–19488. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Oda H, Okamoto I, Murphy N, Chu J, Price SM, Shen MM, Torres-Padilla ME, Heard E and Reinberg D: Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development. Mol Cell Biol. 29:2278–2295. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Li Z, Nie F, Wang S and Li L: Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation. Proc Natl Acad Sci USA. 108:3116–3123. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Wu S, Wang W, Kong X, Congdon LM, Yokomori K, Kirschner MW and Rice JC: Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev. 24:2531–2542. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Jørgensen S, Elvers I, Trelle MB, Menzel T, Eskildsen M, Jensen ON, Helleday T, Helin K and Sørensen CS: The histone methyltransferase SET8 is required for S-phase progression. J Cell Biol. 179:1337–1345. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Congdon LM, Houston SI, Veerappan CS, Spektor TM and Rice JC: PR-Set7-mediated monomethylation of histone H4 lysine 20 at specific genomic regions induces transcriptional repression. J Cell Biochem. 110:609–619. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Abbas T, Shibata E, Park J, Jha S, Karnani N and Dutta A: CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Mol Cell. 40:9–21. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Stopa N, Krebs JE and Shechter D: The PRMT5 arginine methyltransferase: Many roles in development, cancer and beyond. Cell Mol Life Sci. 72:2041–2059. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Yang Y and Bedford MT: Protein arginine methyltransferases and cancer. Nat Rev Cancer. 13:37–50. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Pal S, Vishwanath SN, Erdjument-Bromage H, Tempst P and Sif S: Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. Mol Cell Biol. 24:9630–9645. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Pal S, Baiocchi RA, Byrd JC, Grever MR, Jacob ST and Sif S: Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. EMBO J. 26:3558–3569. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Karkhanis V, Hu YJ, Baiocchi RA, Imbalzano AN and Sif S: Versatility of PRMT5-induced methylation in growth control and development. Trends Biochem Sci. 36:633–641. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Wei TY, Juan CC, Hisa JY, Su LJ, Lee YC, Chou HY, Chen JM, Wu YC, Chiu SC, Hsu CP, et al: Protein arginine methyltransferase 5 is a potential oncoprotein that upregulates G1 cyclins/cyclin-dependent kinases and the phosphoinositide 3-kinase/AKT signaling cascade. Cancer Sci. 103:1640–1650. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Bernstein BE, Meissner A and Lander ES: The mammalian epigenome. Cell. 128:669–681. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Strahl BD and Allis CD: The language of covalent histone modifications. Nature. 403:41–45. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Zhang Y and Reinberg D: Transcription regulation by histone methylation: Interplay between different covalent modifications of the core histone tails. Genes Dev. 15:2343–2360. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Qian YB, Zhang JB, Wu WZ, Fang HB, Jia WD, Zhuang PY, Zhang BH, Pan Q, Xu Y, Wang L, et al: P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma. Cancer. 107:1562–1569. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Bruix J and Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology. 42:1208–1236. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, Sugawara Y, Minagawa M, Takayama T, Kawasaki S and Makuuchi M: Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 38:200–207. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA, Kammula US, Chen Y, Qin LX, Tang ZY and Wang XW: Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell. 10:99–111. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M and Kurdistani SK: Global histone modification patterns predict risk of prostate cancer recurrence. Nature. 435:1262–1266. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Jenuwein T and Allis CD: Translating the histone code. Science. 293:1074–1080. 2001. View Article : Google Scholar : PubMed/NCBI

31 

Cheng D, Yadav N, King RW, Swanson MS, Weinstein EJ and Bedford MT: Small molecule regulators of protein arginine methyltransferases. J Biol Chem. 279:23892–23899. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Zhang B, Dong S, Li Z, Lu L, Zhang S, Chen X, Cen X and Wu Y: Targeting protein arginine methyltransferase 5 inhibits human hepatocellular carcinoma growth via the downregulation of beta-catenin. J Transl Med. 13:3492015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lin Z, Jia H, Hong L, Zheng Y, Shao W, Ren X, Zhu W, Lu L, Lu M, Zhang J, Zhang J, et al: Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection. Oncol Lett 16: 3665-3673, 2018.
APA
Lin, Z., Jia, H., Hong, L., Zheng, Y., Shao, W., Ren, X. ... Chen, J. (2018). Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection. Oncology Letters, 16, 3665-3673. https://doi.org/10.3892/ol.2018.9083
MLA
Lin, Z., Jia, H., Hong, L., Zheng, Y., Shao, W., Ren, X., Zhu, W., Lu, L., Lu, M., Zhang, J., Chen, J."Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection". Oncology Letters 16.3 (2018): 3665-3673.
Chicago
Lin, Z., Jia, H., Hong, L., Zheng, Y., Shao, W., Ren, X., Zhu, W., Lu, L., Lu, M., Zhang, J., Chen, J."Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection". Oncology Letters 16, no. 3 (2018): 3665-3673. https://doi.org/10.3892/ol.2018.9083
Copy and paste a formatted citation
x
Spandidos Publications style
Lin Z, Jia H, Hong L, Zheng Y, Shao W, Ren X, Zhu W, Lu L, Lu M, Zhang J, Zhang J, et al: Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection. Oncol Lett 16: 3665-3673, 2018.
APA
Lin, Z., Jia, H., Hong, L., Zheng, Y., Shao, W., Ren, X. ... Chen, J. (2018). Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection. Oncology Letters, 16, 3665-3673. https://doi.org/10.3892/ol.2018.9083
MLA
Lin, Z., Jia, H., Hong, L., Zheng, Y., Shao, W., Ren, X., Zhu, W., Lu, L., Lu, M., Zhang, J., Chen, J."Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection". Oncology Letters 16.3 (2018): 3665-3673.
Chicago
Lin, Z., Jia, H., Hong, L., Zheng, Y., Shao, W., Ren, X., Zhu, W., Lu, L., Lu, M., Zhang, J., Chen, J."Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection". Oncology Letters 16, no. 3 (2018): 3665-3673. https://doi.org/10.3892/ol.2018.9083
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