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Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma

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Summary

Cancer testis (CT) antigens have received particular attention in cancer immunotherapy. OY-TES-1 is a member of CT antigens. This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma (HCC). OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR (RT-PCR). Of the 56 cases of HCC tissues tested, 37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR. OY-TES-1 protein was subsequently observed on a panel of tissue microarrays. Sera from patients were tested for OY-TES-1 antibody by ELISA. To identify OY-TES-1 capable of inducing cellular immune response, OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro. The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56 (73.21%) HCC tissues, whereas none in 5 normal liver tissues. OY-TES-1 mRNA was frequently expressed not only in HCC tissues (72.97%, 27/37), but also in paired adjacent non-cancer tissues (64.86%, 24/37). But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues (0.76854 vs. 0.09834, P=0.021). Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues, and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues. Seropositivity was detected in 10 of the 45 HCC patients, but not detected in 17 cirrhosis patients and 76 healthy donors. The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2+ HCC cell line which expressed OY-TES-1. The target lysis was mainly HLA class I -dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule. In summary, OY-TES-1 expression is up-regulated in HCC tissues and can be recognized by humoral and cellular responses, which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

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References

  1. Akinyemiju T, Abera S, Ahmed M, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol, 2017,3(12):1683–1691

    Article  Google Scholar 

  2. Zhu J, Yin T, Xu Y, et al. Therapeutics for advanced hepatocellular carcinoma: Recent advances, current dilemma, and future directions. J Cell Physiol, 2019,234(8):12 122–12 132

    Article  CAS  Google Scholar 

  3. Pardee AD, Butterfield LH. Immunotherapy of hepatocellular carcinoma: Unique challenges and clinical opportunities. Oncoimmunology, 2012,1(1):48–55

    Article  Google Scholar 

  4. Sun JY, Yin T, Zhang XY, et al. Therapeutic advances for patients with intermediate hepatocellular carcinoma. J Cell Physiol, 2019,234(8):12 116–12 121

    Article  CAS  Google Scholar 

  5. Wang C, Gu Y, Zhang K, et al. Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types. Nat Commun, 2016,7:10 499

    Article  CAS  Google Scholar 

  6. Seifi-Alan M, Shamsi R, Ghafouri-Fard S. Application of cancer-testis antigens in immunotherapy of hepatocellular carcinoma. Immunotherapy, 2018,10(5):411–421

    Article  CAS  Google Scholar 

  7. Liu C, Luo B, Xie XX, et al. Involvement of X-chromosome reactivation in augmenting cancer testis antigens expression: a hypothesis. Cur Med Sci, 2018,38(1):19–25

    Article  CAS  Google Scholar 

  8. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun, 2004,4:1

    PubMed  Google Scholar 

  9. Almeida LG, Sakabe NJ, de Oliveira AR, et al. CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens. Nucleic Acids Res, 2009,37:D816–D819

    Article  CAS  Google Scholar 

  10. Gordeeva O. Cancer-testis antigens: Unique cancer stem cell biomarkers and targets for cancer therapy. Semin Cancer Biol, 2018,53:75–89

    Article  CAS  Google Scholar 

  11. Caballero OL, Chen YT. Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci, 2009,100(11):2014–2021

    Article  CAS  Google Scholar 

  12. Salmaninejad A, Zamani MR, Pourvahedi M, et al. Cancer/testis antigens: expression, regulation, tumor invasion, and use in immunotherapy of cancers. Immunol Invest, 2016,45(7):619–640

    Article  CAS  Google Scholar 

  13. Ono T, Kurashige T, Harada N, et al. Identification binding protein sp32 precursor as a human cancer/testis antigen. Proc Natl Acad Sci USA, 2001,98(6):3282–3287

    Article  CAS  Google Scholar 

  14. Tammela J, Uenaka A, Ono T, et al. OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer. Int J Oncol, 2006,29(4):903–910

    CAS  PubMed  Google Scholar 

  15. Luo B, Yun X, Fan R, et al. Cancer testis antigen OY-TES-1 expression and serum immunogenicity in colorectal cancer: its relationship to clinicopathological parameters. Int J Clin Exp Pathol, 2013,6(12):2835–2845

    PubMed  PubMed Central  Google Scholar 

  16. Fan R, Huang W, Luo B, et al. Cancer testis antigen OY-TES-1: analysis of protein expression in ovarian cancer with tissue microarrays. Eur J Gynaecol Oncol, 2015,36(3):298–303

    CAS  PubMed  Google Scholar 

  17. Li X, Yan J, Fan R, et al. Serum immunoreactivity of cancer/testis antigen OY-TES-1 and its tissues expression in glioma. Oncol Lett, 2017,13(5):3080–3086

    Article  CAS  Google Scholar 

  18. Okumura H, Noguchi Y, Uenaka A, et al. Identification of an HLA-A24-restricted OY-TES-1 epitope recognized by cytotoxic T-cells. Microbiol Immunol, 2005,49(11):1009–1016

    Article  CAS  Google Scholar 

  19. Greene FL, Page DL, Fleming ID, eds. AJCC cancer staging manual. 6th edition. Chicago: Springer, 2002

    Google Scholar 

  20. Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer, 1954,7(3):462–503

    Article  CAS  Google Scholar 

  21. Paradis V. Histopathology of hepatocellular carcinoma. Recent Results Cancer Res, 2013,190:21–32

    Article  Google Scholar 

  22. Cen Y, Guo W, Luo B, et al. Knockdown of OY-TES-1 by RNAi causes cell cycle arrest and migration decrease in bone marrow derived mesenchymal stem cells. Cell Biol Int, 2012,36(10):917–922

    Article  CAS  Google Scholar 

  23. de Kok JB, Roelofs RW, Giesendorf BA, et al. Normalization of gene expression measurements in tumor tissues: comparison of 13 endogenous control genes. Lab Invest, 2005,85(1):154–159

    Article  CAS  Google Scholar 

  24. Luo C, Xiao X, Liu D, et al. CABYR is a novel cancer-testis antigen in lung cancer. Clin Cancer Res, 2007,13(4):1288–1297

    Article  CAS  Google Scholar 

  25. Riener MO, Wild PJ, Soll C, et al. Frequent expression of the novel cancer testis antigen MAGE-C2/CT-10 in hepatocellular carcinoma. Int J Cancer, 2009,124(2):352–357

    Article  CAS  Google Scholar 

  26. Mathieu MG, Linley AJ, Reeder SP, et al. HAGE, a cancer/testis antigen expressed at the protein level in a variety of cancers. Cancer Immun, 2010,10:2

    PubMed  PubMed Central  Google Scholar 

  27. Yokoe T, Tanaka F, Mimori K, et al. Efficient identification of a novel cancer/testis antigen for immunotherapy using three-step microarray analysis. Cancer Res, 2008,68(4):1074–1082

    Article  CAS  Google Scholar 

  28. Fu J, Luo B, Guo WW, et al. Down-regulation of cancer/ testis antigen OY-TES-1 attenuates malignant behaviors of hepatocellular carcinoma cells in vitro. Int J Clin Exp Pathol, 2015,8(7):7786–7797

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Hu Q, Fu J, Luo B, et al. OY-TES-1 may regulate the malignant behavior of liver cancer via NANOG, CD9, CCND2 and CDCA3: a bioinformatic analysis combine with RNAi and oligonucleotide microarray. Oncol Rep, 2015,33(4):1965–1975

    Article  CAS  Google Scholar 

  30. Grizzi F, Franceschini B, Hamrick C, et al. Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma. J Transl Med, 2007,5:3

    Article  Google Scholar 

  31. Johnson PJ. The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis, 2001,5(1):145–159

    Article  CAS  Google Scholar 

  32. Chang TS, Wu YC, Tung SY, et al. Alpha-fetoprotein measurement benefits hepatocellular carcinoma surveillance in patients with cirrhosis. Am J Gastroenterol, 2015,110(6):836–844

    Article  CAS  Google Scholar 

  33. Thomas R, Al-Khadam G, Roelands J, et al. NY-ESO-1 based immunotherapy of cancer: current perspectives. Front Immunol, 2018,9:947

    Article  Google Scholar 

  34. Schooten E, Di Maggio A, van Bergen En Henegouwen PMP, et al. MAGE-A antigens as targets for cancer immunotherapy. Cancer Treat Rev, 2018,67:54–62

    Article  CAS  Google Scholar 

  35. Faramarzi S, Ghafouri-Fard S. Melanoma: a prototype of cancer-testis antigen-expressing malignancies. Immunotherapy, 2017,9(13):1103–1113

    Article  CAS  Google Scholar 

Download references

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Author notes

  1. The Authors contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, China

    Bin Luo, Yong-da Lin, Ying-ying Ge, Xia Zeng, Shui-qing Bi, Wei-xia Nong, Qing-mei Zhang & Xiao-xun Xie

  2. Department of Surgery, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China

    Xiang Yun & Chang Liu

  3. Clinical Laboratory, Chinese Medicine Hospital, Quanzhou, 362000, China

    Jing Li

  4. School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning, 530021, China

    Rong Fan

  5. Department of Pathology, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China

    Wen-wen Guo

  6. Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, 530021, China

    Xiao-xun Xie

  7. Key Laboratory Research on Preclinical Medicine, Guangxi Medical University, Nanning, 530021, China

    Xiao-xun Xie

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  1. Bin Luo
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Corresponding authors

Correspondence to Wei-xia Nong, Qing-mei Zhang or Xiao-xun Xie.

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Additional information

This work was supported by grants from the National Natural Science Foundation of China (No. 81860445, No. 81960453, No. 81560408, and No. 81660429), Natural Science Foundation of Guangxi Province (No. 2016GXNSFBA380159, No. 2018GXNSFAA281251, No. 2018GXNSFAA050151, No. 2017GXNSFAA198001, No. 2018GXNSFAA281050, and No. 2018GXNSFBA281187), Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University) and Ministry of Education (No. GK2018-09, No. GKE 2019-08, and No. K2015-TKF03), and Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi Province (No. 2018KY0109).

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Luo, B., Yun, X., Li, J. et al. Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma. CURR MED SCI 40, 719–728 (2020). https://doi.org/10.1007/s11596-020-2241-x

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  • DOI: https://doi.org/10.1007/s11596-020-2241-x

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