Skip to main content

Advertisement

SpringerLink
Log in

SUV39H1 is a prognosis and immune microenvironment-related biomarker in diffuse large B-cell lymphoma

  • RESEARCH ARTICLE
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Background

The tumor microenvironment plays a crucial role in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase Suppressor of variegation 3-9 homolog 1 (SUV39H1) is a significant gene that promotes the progression of various malignancies. However, the specific expression of SUV39H1 in DLBCL remains unclear.

Methods

By retrieving data from GEPIA, UCSC XENA and TCGA public databases, we observed the high expression of SUV39H1 in DLBCL. Combined with an immunohistochemical validation assay, we analyzed our hospital’s clinical characteristics and prognosis of 67 DLBCL patients. The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. Furthermore, the experiments in vitro were deployed to evaluate the regulation of SUV39H1 on the DLBCL immune microenvironment.

Results

The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. The prognostic analysis showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P < 0.05). We further discovered that SUV39H1 upregulated the expression of CD86+ and CD163+ tumor-associated macrophages by DLBCL patients’ tissues and cell experiments in vitro (P < 0.05). And SUV39H1-associated T lymphocyte subsets and cytokines IL-6/CCL-2 were downregulated in DLBCL (P < 0.05).

Conclusions

In summary, SUV39H1 might be not only a potential target for treating DLBCL but also a clinical indicator for doctors to evaluate the trend of disease development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The datasets supporting the conclusions of this article are available in the Oncomine (https://www.oncomine.org/resource/login.html), Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/), Cancer Cell Line Encyclopedia (CCLE, https://portals.broadinstitute.org/ccle/), UALCAN (http://ualcan.path.uab.edu/), and The Cancer Genome Atlas (TCGA, https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) databases.

References

  1. Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016;66(6):443–59.

    Article  PubMed  Google Scholar 

  2. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.

    Article  CAS  PubMed  Google Scholar 

  3. Xu PP, Fu D, Li JY, Hu JD, Wang X, Zhou JF, et al. Anthracycline dose optimisation in patients with diffuse large B-cell lymphoma: a multicentre, phase 3, randomised, controlled trial. Lancet Haematol. 2019;6(6):e328–37.

    Article  PubMed  Google Scholar 

  4. Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018;50(1):74–87.

    Article  PubMed  Google Scholar 

  5. Bakhshi TJ, Georgel PT. Genetic and epigenetic determinants of diffuse large B-cell lymphoma. Blood Cancer J. 2020;10(12):123.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nielsen SJ, Schneider R, Bauer UM, Bannister AJ, Morrison A, O’Carroll D, et al. Rb targets histone H3 methylation and HP1 to promoters. Nature. 2001;412(6846):561–5.

    Article  CAS  PubMed  Google Scholar 

  7. Dodge JE, Kang YK, Beppu H, Lei H, Li E. Histone H3–K9 methyltransferase ESET is essential for early development. Mol Cell Biol. 2004;24(6):2478–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Peters AH, O’Carroll D, Scherthan H, Mechtler K, Sauer S, Schöfer C, et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell. 2001;107(3):323–37.

    Article  CAS  PubMed  Google Scholar 

  9. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature. 2005;436(7051):660–5.

    Article  CAS  PubMed  Google Scholar 

  10. Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, Yu Y, et al. Senescence-associated reprogramming promotes cancer stemness. Nature. 2018;553(7686):96–100.

    Article  CAS  PubMed  Google Scholar 

  11. Pace L, Goudot C, Zueva E, Gueguen P, Burgdorf N, Waterfall JJ, et al. The epigenetic control of stemness in CD8(+) T cell fate commitment. Science. 2018;359(6372):177–86.

    Article  CAS  PubMed  Google Scholar 

  12. Shen JZ, Qiu Z, Wu Q, Finlay D, Garcia G, Sun D, et al. FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells. Cell. 2021;184(2):352-369.e23.

    Article  CAS  PubMed  Google Scholar 

  13. Altieri F, Di Stadio CS, Federico A, Miselli G, De Palma M, Rippa E, et al. Epigenetic alterations of gastrokine 1 gene expression in gastric cancer. Oncotarget. 2017;8(10):16899–911.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chiba T, Saito T, Yuki K, Zen Y, Koide S, Kanogawa N, et al. Histone lysine methyltransferase SUV39H1 is a potent target for epigenetic therapy of hepatocellular carcinoma. Int J Cancer. 2015;136(2):289–98.

    Article  CAS  PubMed  Google Scholar 

  15. Lu C, Yang D, Klement JD, Oh IK, Savage NM, Waller JL, et al. SUV39H1 represses the expression of cytotoxic T-lymphocyte effector genes to promote colon tumor immune evasion. Cancer Immunol Res. 2019;7(3):414–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mo W, Liu Q, Lin CC, Dai H, Peng Y, Liang Y, et al. mtor inhibitors suppress homologous recombination repair and synergize with PARP inhibitors via regulating SUV39H1 in BRCA-proficient triple-negative breast cancer. Clin Cancer Res. 2016;22(7):1699–712.

    Article  CAS  PubMed  Google Scholar 

  17. Schleich K, Kase J, Dörr JR, Trescher S, Bhattacharya A, Yu Y, et al. H3K9me3-mediated epigenetic regulation of senescence in mice predicts outcome of lymphoma patients. Nat Commun. 2020;11(1):3651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Vivian J, Rao AA, Nothaft FA, Ketchum C, Armstrong J, Novak A, et al. Toil enables reproducible, open source, big biomedical data analyses [J]. Nat Biotechnol. 2017;35(4):314–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Friedrichs K, Gluba S, Eidtmann H, Jonat W. Overexpression of p53 and prognosis in breast cancer. Cancer. 1993;72(12):3641–7.

    Article  CAS  PubMed  Google Scholar 

  21. Remmele W, Stegner HE. Immunhistochemischer Nachweis von Ostrogenrezeptoren (ERICA) in Mammakarzinomgewebe: Vorschlag zur einheitlichen Formulierung des Untersuchungs-befundes. Dtsch Arztebl. 1986;83:3362–4.

    Google Scholar 

  22. Wang J, Yin X, He W, Xue W, Zhang J, Huang Y. SUV39H1 deficiency suppresses clear cell renal cell carcinoma growth by inducing ferroptosis. Acta Pharm Sin B. 2021;11(2):406–19.

    Article  CAS  PubMed  Google Scholar 

  23. Djeghloul D, Kuranda K, Kuzniak I, Barbieri D, Naguibneva I, Choisy C, et al. Age-associated decrease of the histone methyltransferase SUV39H1 in HSC perturbs heterochromatin and B lymphoid differentiation. Stem Cell Rep. 2016;6(6):970–84.

    Article  CAS  Google Scholar 

  24. Boonmee A, Benjaskulluecha S, Kueanjinda P, Wongprom B, Pattarakankul T, Palaga T. The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications. Sci Rep. 2021;11(1):21574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chen TT, Wu SM, Ho SC, Chuang HC, Liu CY, Chan YF, et al. SUV39H1 reduction is implicated in abnormal inflammation in COPD. Sci Rep. 2017;7:46667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang J, Yan W, Peng X, Jiang Y, He L, Peng Y, et al. Functional role of SUV39H1 in human renal tubular epithelial cells under high-glucose ambiance. Inflammation. 2018;41(1):1–10.

    Article  PubMed  Google Scholar 

  27. Sudhahar V, Das A, Horimatsu T, Ash D, Leanhart S, Antipova O, et al. Copper transporter ATP7A (copper-transporting P-type ATPase/Menkes ATPase) limits vascular inflammation and aortic aneurysm development: role of microRNA-125b. Arterioscler Thromb Vasc Biol. 2019;39(11):2320–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Weng X, Zhang Y, Li Z, Yu L, Xu F, Fang M, et al. Class II transactivator (CIITA) mediates IFN-γ induced eNOS repression by enlisting SUV39H1. Biochim Biophys Acta Gene Regul Mech. 2019;1862(2):163–72.

    Article  CAS  PubMed  Google Scholar 

  29. Reimann M, Lee S, Loddenkemper C, Dörr JR, Tabor V, Aichele P, et al. Tumor stroma-derived TGF-beta limits myc-driven lymphomagenesis via Suv39h1-dependent senescence. Cancer Cell. 2010;17(3):262–72.

    Article  CAS  PubMed  Google Scholar 

  30. Iordanskiy S, Van Duyne R, Sampey GC, Woodson CM, Fry K, Saifuddin M, et al. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells. Virology. 2015;485:1–15.

    Article  CAS  PubMed  Google Scholar 

  31. Dörr JR, Yu Y, Milanovic M, Beuster G, Zasada C, Däbritz JH, et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature. 2013;501(7467):421–5.

    Article  PubMed  Google Scholar 

  32. Harro CM, Perez-Sanz J, Costich TL, Payne KK, Anadon CM, Chaurio RA, et al. Methyltransferase inhibitors restore SATB1 protective activity against cutaneous T cell lymphoma in mice. J Clin Invest. 2021;131(3): e135711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Campaner S, Doni M, Verrecchia A, Fagà G, Bianchi L, Amati B. Myc, Cdk2 and cellular senescence: old players, new game. Cell Cycle. 2010;9(18):3655–61.

    Article  CAS  PubMed  Google Scholar 

  34. Park JW, Bae YS. Dephosphorylation of p53 Ser 392 enhances trimethylation of histone H3 Lys 9 via SUV39h1 stabilization in CK2 downregulation-mediated senescence. Mol Cells. 2019;42(11):773–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Fane M, Weeraratna AT. How the ageing microenvironment influences tumour progression. Nat Rev Cancer. 2020;20(2):89–106.

    Article  CAS  PubMed  Google Scholar 

  36. Ochi Y, Kazuma Y, Hiramoto N, Ono Y, Yoshioka S, Yonetani N, et al. Utility of a simple prognostic stratification based on platelet counts and serum albumin levels in elderly patients with diffuse large B cell lymphoma. Ann Hematol. 2017;96(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  37. Pace L, Goudot C, Zueva E, Gueguen P, Burgdorf N, Waterfall JJ, et al. The epigenetic control of stemness in CD8+ T cell fate commitment. Science. 2018;359(6372):177–86.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 82070210) and Henan Provincial Science and Technology Research Project (Grant No. SBGJ202001008).

Author information

Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Yue Zhang, Siyu Qian, Qing Wen, Yaxin Lei, Jingjing Ge, Xiaoshuang Kong, Wenhua Wang, Zeyuan Wang, Shaoxuan Wu, Mingzhi Zhang, Xudong Zhang & Qingjiang Chen

  2. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Guannan Wang & Wencai Li

  3. Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, China

    Huting Hou & Canwei Tang

  4. Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, China

    Yue Zhang & Siyu Qian

Authors
  1. Yue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siyu Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yaxin Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jingjing Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaoshuang Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wenhua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zeyuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Huting Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Canwei Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shaoxuan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Guannan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Wencai Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Mingzhi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Xudong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Qingjiang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Data curation, YZ, SQ, QW, YL, JG, XK, WW, ZW, HH and SW; Funding acquisition, MZ, XZ and QC; Investigation, YZ and SQ; Methodology, MZ and XZ; Resources, GW and WL; Software, YZ and CT; Supervision, MZ, XZ and QC; Writing—original draft, YZ; Writing—review and editing, QC. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xudong Zhang or Qingjiang Chen.

Ethics declarations

Conflict of interest

All the authors declare that they have no competing interests.

Ethical approval

The use of pathological specimens and clinical information of patients was approved by the Ethics Committee of Scientific Research and Clinical Trial of The First Affiliated Hospital of Zhengzhou University (approval no. 2022-KY-0038-002; Zhengzhou, China).

Consent to participate

The consents to participate in this study was provided by all the participants. This research has obtained the consent of all the participants. The privacy rights of human subjects must always be observed by all the authors.

Consent for publication

All the authors have read and consented to submit the article to this journal.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yue Zhang and Siyu Qian are the two first authors.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 KB)

Supplementary file2 (XLSX 13 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Qian, S., Wen, Q. et al. SUV39H1 is a prognosis and immune microenvironment-related biomarker in diffuse large B-cell lymphoma. Clin Transl Oncol 25, 2438–2450 (2023). https://doi.org/10.1007/s12094-023-03128-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-023-03128-2

Keywords

Search

Navigation