DOI QR코드

DOI QR Code

Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

  • Piao, Yong-Rui (Department of Urology, Affiliated Hospital of YanBian University) ;
  • Piao, Long-Zhen (Department of Oncology, Affiliated Hospital of YanBian University) ;
  • Zhu, Lian-Hua (Department of Dermatology and Venereology, Affiliated Hospital of YanBian University) ;
  • Jin, Zhe-Hu (Department of Dermatology and Venereology, Affiliated Hospital of YanBian University) ;
  • Dong, Xiu-Zhe (Department of Urology, Affiliated Hospital of YanBian University)
  • Published : 2013.06.30

Abstract

Background: Optimal treatment for prostate cancer remains a challenge worldwide. Recently, T cell immunoglobulin mucin-3 (TIM-3) has been implicated in tumor biology but its contribution prostate cancer remains unclear. The aim of this study was to investigate the role of TIM-3 as a prognostic marker in patients with prostate cancer. Methods: TIM-3 protein expression was determined by immunohistochemistry and Western blotting in 137 prostate cancer tumor samples and paired adjacent benign tissue. We also performed cell proliferation assays using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl- 2H tetrazolium bromide (MTT) and cell invasion assays. The effects of small interfering RNA (siRNA)-mediated knockdown of TIM-3 (TIM-3 siRNA) in two human prostate cancer cell lines were also evaluated. Results: TIM-3 expression was higher in prostate cancer tissue than in the adjacent benign tissue (P<0.001). High TIM-3 expression was an independent predictor of both recurrence-free survival and progression-free survival. TIM-3 protein was expressed in both prostate cancer cell lines and knockdown suppressed their proliferation and invasion capacity. Conclusions: TIM-3 expression is associated with a poor prognosis in prostate cancer. Taken together, our resutlts indicate that TIM-3 is a potential prognostic marker in prostate cancer.

Keywords

TIM-3;prostate cancer;prognosis;biomarker

Acknowledgement

Supported by : Yan Bian University Science and Technology

References

  1. Abildgaard MO, Borre M, Mortensen MM, et al (2012). Downregulation of zinc finger protein 132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis. Int J Cancer, 130, 885-95. https://doi.org/10.1002/ijc.26097
  2. Cai C, Wang L, Wu Z, et al (2012). T-cell immunoglobulin- and mucin-domain- containing molecule 3 gene polymorphisms and renal cell carcinoma. DNA Cell Biol, 31, 1285-9. https://doi.org/10.1089/dna.2012.1625
  3. Facompre N, El-Bayoumy K (2009).Potential stages for prostate cancer prevention with selenium: implications for cancer survivors. Cancer Res, 69, 2699-703. https://doi.org/10.1158/0008-5472.CAN-08-4359
  4. Fourcade J, Sun Z, Benallaoua M, et al (2010). Upregulation of Tim-3 and PD-1 expression is associated with tumor antigenspecific CD8+T cell dysfunction in melanoma patients. J Exp Med, 207, 2175-86. https://doi.org/10.1084/jem.20100637
  5. Geng H, Zhang GM, Li D, et al (2006). Soluble form of T cell Ig mucin 3 is an inhibitory molecule in T cell-mediated immune response. J Immunol, 176, 1411-20. https://doi.org/10.4049/jimmunol.176.3.1411
  6. Huang X, Bai X, Cao Y, et al (2010). Lymphoma endothelium preferentially expresses TIM-3 and facilitates the progression of lymphoma by mediating immune evasion. J Exp Med, 207, 505-20. https://doi.org/10.1084/jem.20090397
  7. Jan M, Chao MP, Cha AC, et al (2011). Prospective separation of normal and leukemic stem cells based on differential expression of Tim-3, a human acute myeloid leukemia stem cell marker. Proc Natl Acad Sci, 108, 5009-14. https://doi.org/10.1073/pnas.1100551108
  8. Jemal A, Siegel R, Xu J, Ward E (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  9. Kikushige Y, Shima T, Takayanagi S, et al (2010). Tim-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell, 7, 708-17. https://doi.org/10.1016/j.stem.2010.11.014
  10. Sakuishi K, Apetoh L, Sullivan JM, et al (2010). Targeting TIM-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med, 207, 2187-94. https://doi.org/10.1084/jem.20100643
  11. Sugiyama Y, Masumori N, Fukuta F, et al (2013). Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. Asian Pac J Cancer Prev, 14, 1-4. https://doi.org/10.7314/APJCP.2013.14.1.1
  12. Wiener Z, Kohalmi B, Pocza P, et al (2007). TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells. J Invest Dermatol, 127, 906-14. https://doi.org/10.1038/sj.jid.5700616
  13. Xu LW, Qian M, Jia RP, et al (2012). Expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer. Asian Pac J Cancer Prev, 13, 1639-44. https://doi.org/10.7314/APJCP.2012.13.4.1639
  14. Yang X, Liang L, Zhang XF, et al (2013). MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting IL-6-Stat3 pathway. Hepatology, 58, 158-70. https://doi.org/10.1002/hep.26305
  15. Yun UJ, Park SE, Jo YS, Kim J, Shin DY (2012). DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors. Cancer Lett, 323, 155-60. https://doi.org/10.1016/j.canlet.2012.04.003
  16. Zhuang X, Zhang X, Xia X, et al (2012). Ectopic expression of TIM-3 in lung cancers: a potential independent prognostic factor for patients with NSCLC. Am J Clin Pathol, 137, 978 - 85. https://doi.org/10.1309/AJCP9Q6OVLVSHTMY

Cited by

  1. Impact of Allogenic and Autologous Transfusion on Immune Function in Patients with Tumors vol.15, pp.1, 2014, https://doi.org/10.7314/APJCP.2014.15.1.467
  2. Association between polymorphisms in the promoter region of T cell immunoglobulin and mucin domain-3 and myasthenia gravis-associated thymoma pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.2845
  3. Tim-3 is upregulated in human colorectal carcinoma and associated with tumor progression vol.15, pp.2, 2016, https://doi.org/10.3892/mmr.2016.6065
  4. Tim-3 and its role in regulating anti-tumor immunity vol.276, pp.1, 2017, https://doi.org/10.1111/imr.12520
  5. TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner vol.113, pp.10, 2015, https://doi.org/10.1038/bjc.2015.323
  6. T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma: Clinicopathologic correlations and association with survival vol.112, pp.4, 2015, https://doi.org/10.1002/jso.24012
  7. Profiling Immune Escape in Hodgkin’s and Diffuse large B-Cell Lymphomas Using the Transcriptome and Immunostaining vol.10, pp.11, 2018, https://doi.org/10.3390/cancers10110415
  8. Tumor cell-intrinsic Tim-3 promotes liver cancer via NF-κB/IL-6/STAT3 axis vol.37, pp.18, 2018, https://doi.org/10.1038/s41388-018-0140-4
  9. Immune Checkpoint-Mediated Interactions Between Cancer and Immune Cells in Prostate Adenocarcinoma and Melanoma vol.9, pp.1664-3224, 2018, https://doi.org/10.3389/fimmu.2018.01786
  10. Differential expression of TIM-3 between primary and metastatic sites in renal cell carcinoma vol.19, pp.1, 2019, https://doi.org/10.1186/s12885-019-5273-5