Skip to main content

Advertisement

SpringerLink
Log in

Decreased DIO3OS Expression Predicts Poor Prognosis in Hepatocellular Carcinoma and is Associated with Immune Infiltration

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Hepatocellular carcinoma has become one of the most shared cancers in the whole world because of its high morbidity, poor survival rate, and low recovery rate. LncRNA DIO3 opposite strand upstream RNA (DIO3OS) has been reported to be obviously important in several human cancers, while its biological function in hepatocellular carcinoma (HCC) remains unclear. Here, DIO3OS gene expression data and clinical information of HCC patients were extracted from the Cancer Genome Atlas (TCGA) database and the university of California Santa Cruz (UCSC) Xena database. In our study, the Wilcoxon rank sum test was used to compare DIO3OS expression between healthy individuals and HCC patients. It was found that patients with HCC had significantly lower DIO3OS expression than healthy individuals. Furthermore, Kaplan–Meier curves and Cox regression analysis showed that high DIO3OS expression tended to predict better prognosis and higher survival rate in HCC patients. In addition, the gene set enrichment analysis (GSEA) assay was used to annotate the biological function of DIO3OS. It was found that DIO3OS was significantly correlated with immune invasion in HCC. This was also aided by the subsequent ESTIMATE assay. Our study provides a novel biomarker and therapeutic strategy for patients with hepatocellular carcinoma.

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

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are from the public database. And, all experimental protocols were performed in accordance with relevant guidelines.

References

  • Amon L et al (2019) Transcriptional control of dendritic cell development and functions. Int Rev Cell Mol Biol 349:55–151

    Article  CAS  PubMed  Google Scholar 

  • Arneth B (2019) Tumor microenvironment. Medicina (kaunas) 56(1):15

    Article  PubMed  Google Scholar 

  • Bindea G et al (2013) Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 39(4):782–795

    Article  CAS  PubMed  Google Scholar 

  • Bödder J et al (2020) Harnessing the cDC1-NK cross-talk in the tumor microenvironment to battle cancer. Front Immunol 11:631713

    Article  PubMed  Google Scholar 

  • Böttcher JP et al (2018) NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 172(5):1022-1037.e1014

    Article  PubMed  PubMed Central  Google Scholar 

  • Cao X et al (2007) Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 27(4):635–646

    Article  CAS  PubMed  Google Scholar 

  • Chen W et al (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66(2):115–132

    Article  PubMed  Google Scholar 

  • Cui K et al (2019) Long noncoding RNA DIO3OS interacts with miR-122 to promote proliferation and invasion of pancreatic cancer cells through upregulating ALDOA. Cancer Cell Int 19:202

    Article  PubMed  PubMed Central  Google Scholar 

  • Echarti A et al (2019) CD8+ and regulatory T cells differentiate tumor immune phenotypes and predict survival in locally advanced head and neck cancer. Cancers 11(9):1398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Serag HB (2011) Hepatocellular carcinoma. N Engl J Med 365(12):1118–1127

    Article  CAS  PubMed  Google Scholar 

  • El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557–2576

    Article  CAS  PubMed  Google Scholar 

  • Farhood B et al (2020) TGF-β in radiotherapy: mechanisms of tumor resistance and normal tissues injury. Pharmacol Res 155:104745

    Article  CAS  PubMed  Google Scholar 

  • Forner A, Reig M, Bruix J (2018) Hepatocellular carcinoma. The Lancet 391(10127):1301–1314

    Article  Google Scholar 

  • Fregni G et al (2012) NK cells sense tumors, course of disease and treatments: consequences for NK-based therapies. Oncoimmunology 1(1):38–47

    Article  PubMed  PubMed Central  Google Scholar 

  • Global Burden of Disease Cancer C et al (2019) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol 5(12):1749–1768

    Article  Google Scholar 

  • Habif G et al (2019) Targeting natural killer cells in solid tumors. Cell Mol Immunol 16(5):415–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heilig R et al (2003) The DNA sequence and analysis of human chromosome 14. Nature 421(6923):601–607

    Article  CAS  PubMed  Google Scholar 

  • Hernandez A (2005) Structure and function of the type 3 deiodinase gene. Thyroid 15(8):865–874

    Article  CAS  PubMed  Google Scholar 

  • Hernandez A et al (2004) Complex organization and structure of sense and antisense transcripts expressed from the DIO3 gene imprinted locus. Genomics 83(3):413–424

    Article  CAS  PubMed  Google Scholar 

  • Konjević GM et al (2019) The role of cytokines in the regulation of NK cells in the tumor environment. Cytokine 117:30–40

    Article  PubMed  Google Scholar 

  • Liu J et al (2018) An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell 173(2):400-416.e411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marson A et al (2007) Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 445(7130):931–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishikawa H, Sakaguchi S (2010) Regulatory T cells in tumor immunity. Int J Cancer 127(4):759–767

    CAS  PubMed  Google Scholar 

  • Ohue Y, Nishikawa H (2019) Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? Cancer Sci 110(7):2080–2089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parkin DM et al (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94(2):153–156

    Article  CAS  PubMed  Google Scholar 

  • Peterson EE, Barry KC (2020) The natural killer-dendritic cell immune axis in anti-cancer immunity and immunotherapy. Front Immunol 11:621254

    Article  CAS  PubMed  Google Scholar 

  • Piñeiro Fernández J et al (2019) Hepatic tumor microenvironments and effects on NK cell phenotype and function. Int J Mol Sci 20(17):4131

    Article  PubMed  PubMed Central  Google Scholar 

  • Reik W, Walter J (2001) Genomic imprinting: parental influence on the genome. Nat Rev Genet 2(1):21–32

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S et al (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol (baltimore, Md. : 1950) 155(3):1151–1164

    Article  CAS  Google Scholar 

  • Sanchez Calle A et al (2018) Emerging roles of long non-coding RNA in cancer. Cancer Sci 109(7):2093–2100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarhan D et al (2015) Dendritic cell regulation of NK-cell responses involves lymphotoxin-α, IL-12, and TGF-β. Eur J Immunol 45(6):1783–1793

    Article  CAS  PubMed  Google Scholar 

  • Schleypen JS et al (2006) Cytotoxic markers and frequency predict functional capacity of natural killer cells infiltrating renal cell carcinoma. Clin Cancer Res 12(3 Pt 1):718–725

    Article  CAS  PubMed  Google Scholar 

  • Scott KE, Cleveland JL (2016) Lactate wreaks havoc on tumor-infiltrating T and NK cells. Cell Metab 24(5):649–650

    Article  CAS  PubMed  Google Scholar 

  • Song M et al (2019) Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma. Aging 11(22):10422–10453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Struhl K (2007) Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat Struct Mol Biol 14(2):103–105

    Article  CAS  PubMed  Google Scholar 

  • Subramanian A et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102(43):15545–15550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun C et al (2015) NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma. Cell Mol Immunol 12(3):292–302

    Article  CAS  PubMed  Google Scholar 

  • Suuring M, Moreau A (2021) Regulatory macrophages and tolerogenic dendritic cells in myeloid regulatory cell-based therapies. Int J Mol Sci 22(15):7970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z et al (2020a) Glycolysis and oxidative phosphorylation play critical roles in natural killer cell receptor-mediated natural killer cell functions. Front Immunol 11:202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z et al (2020b) Long noncoding RNA DIO3OS hinders cell malignant behaviors of hepatocellular carcinoma cells through the microRNA-328/Hhip axis. Cancer Manag Res 12:3903–3914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M et al (2021) Long non-coding RNA DIO3OS/let-7d/NF-kappaB2 axis regulates cells proliferation and metastasis of thyroid cancer cells. J Cell Commun Signal 15(2):237–250

    Article  CAS  PubMed  Google Scholar 

  • Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23(13):1494–1504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young A et al (2018) A2AR adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment. Can Res 78(4):1003–1016

    Article  CAS  Google Scholar 

  • Zhou X et al (2015) Tissue resident regulatory T cells: novel therapeutic targets for human disease. Cell Mol Immunol 12(5):543–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Thanks to “Xiantao Academic” for their assistance in this study.

Funding

This work was supported by the Natural Science Foundation of Shandong Province (grant nos. ZR2020MH415, ZR2021LZY033).

Author information

Author notes

  1. Yunhan Wang, Ping Sun, and Xinping Hao have contributed equally to this work. Ping Sun and Xinping Hao are co-first authors.

Authors and Affiliations

  1. Department of Pathology and Pathophysiology, Weifang Medical University, Weifang, 261053, Shandong Province, China

    Yunhan Wang, Jiangyue Liu & Daijuan Zhang

  2. Department of Immunology, Weifang Medical University, Weifang, 261053, Shandong Province, China

    Ping Sun

  3. Department of Intensive Care Unit, Weifang Traditional Chinese Medicine Hospital, Weifang, 261041, Shandong Province, China

    Xinping Hao

  4. Dpartment of Pathology, Shanxi Traditional Chinese Medicine Hospital, Taiyuan, 030000, Shanxi Province, China

    Daihong Cao

Authors
  1. Yunhan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ping Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xinping Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daihong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiangyue Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daijuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: YW; Administrative support: DZ; Provision of study materials or patients: XH, PS; Collection and assembly of data: DC, XH, PS; Data analysis and interpretation: YW, JL; Manuscript writing: All authors; Final approval of manuscript: All authors.

Corresponding authors

Correspondence to Jiangyue Liu or Daijuan Zhang.

Ethics declarations

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

10528_2023_10345_MOESM1_ESM.jpg

Supplementary file1 (JPG 4106 KB). Supplement figure. Correlation analysis of multiple immune cell markers and lncRNA DIO3OS.

10528_2023_10345_MOESM2_ESM.jpg

Supplementary file2 (JPG 4847 KB). Supplement figure. Correlation analysis of multiple immune cell markers and lncRNA DIO3OS.

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

Wang, Y., Sun, P., Hao, X. et al. Decreased DIO3OS Expression Predicts Poor Prognosis in Hepatocellular Carcinoma and is Associated with Immune Infiltration. Biochem Genet 61, 1791–1806 (2023). https://doi.org/10.1007/s10528-023-10345-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-023-10345-5

Keywords

Search

Navigation