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Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer

  • Lee, Ji-Hye (Department of Pathology, Soonchunhyang University Cheonan Hospital) ;
  • Son, Myoung-Won (Department of General Surgery, Soonchunhyang University Cheonan Hospital) ;
  • Kim, Kyung-Ju (Department of Pathology, Soonchunhyang University Cheonan Hospital) ;
  • Oh, Mee-Hye (Department of Pathology, Soonchunhyang University Cheonan Hospital) ;
  • Cho, Hyundeuk (Department of Pathology, Soonchunhyang University College of Medicine) ;
  • Lee, Hyun Ju (Department of Pathology, Soonchunhyang University Cheonan Hospital) ;
  • Jang, Si-Hyong (Department of Pathology, Soonchunhyang University Cheonan Hospital) ;
  • Lee, Moon Soo (Department of General Surgery, Soonchunhyang University Cheonan Hospital)
  • Received : 2015.12.21
  • Accepted : 2016.01.28
  • Published : 2016.03.31

Abstract

Purpose: Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods: Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results: In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions: We suggested that TLE1 expression is a good prognostic indicator in GCs.

Keywords

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. https://doi.org/10.3322/caac.20107
  2. Chen G, Courey AJ. Groucho/TLE family proteins and transcriptional repression. Gene 2000;249:1-16. https://doi.org/10.1016/S0378-1119(00)00161-X
  3. Arce L, Pate KT, Waterman ML. Groucho binds two conserved regions of LEF-1 for HDAC-dependent repression. BMC Cancer 2009;9:159. https://doi.org/10.1186/1471-2407-9-159
  4. Ghosh HS, Spencer JV, Ng B, McBurney MW, Robbins PD. Sirt1 interacts with transducin-like enhancer of split-1 to inhibit nuclear factor kappaB-mediated transcription. Biochem J 2007;408:105-111. https://doi.org/10.1042/BJ20070817
  5. Buscarlet M, Hermann R, Lo R, Tang Y, Joachim K, Stifani S. Cofactor-activated phosphorylation is required for inhibition of cortical neuron differentiation by Groucho/TLE1. PLoS One 2009;4:e8107. https://doi.org/10.1371/journal.pone.0008107
  6. Flowers EB, Poole RJ, Tursun B, Bashllari E, Pe'er I, Hobert O. The Groucho ortholog UNC-37 interacts with the short Groucho-like protein LSY-22 to control developmental decisions in C. elegans. Development 2010;137:1799-1805. https://doi.org/10.1242/dev.046219
  7. Allander SV, Illei PB, Chen Y, Antonescu CR, Bittner M, Ladanyi M, et al. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol 2002;161:1587-1595. https://doi.org/10.1016/S0002-9440(10)64437-9
  8. Nagayama S, Katagiri T, Tsunoda T, Hosaka T, Nakashima Y, Araki N, et al. Genome-wide analysis of gene expression in synovial sarcomas using a cDNA microarray. Cancer Res 2002;62:5859-5866.
  9. Jagdis A, Rubin BP, Tubbs RR, Pacheco M, Nielsen TO. Prospective evaluation of TLE1 as a diagnostic immunohistochemical marker in synovial sarcoma. Am J Surg Pathol 2009;33:1743-1751. https://doi.org/10.1097/PAS.0b013e3181b7ed36
  10. Foo WC, Cruise MW, Wick MR, Hornick JL. Immunohistochemical staining for TLE1 distinguishes synovial sarcoma from histologic mimics. Am J Clin Pathol 2011;135:839-844. https://doi.org/10.1309/AJCP45SSNAOPXYXU
  11. Kosemehmetoglu K, Vrana JA, Folpe AL. TLE1 expression is not specific for synovial sarcoma: a whole section study of 163 soft tissue and bone neoplasms. Mod Pathol 2009;22:872-878. https://doi.org/10.1038/modpathol.2009.47
  12. Terry J, Saito T, Subramanian S, Ruttan C, Antonescu CR, Goldblum JR, et al. TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. Am J Surg Pathol 2007;31:240-246. https://doi.org/10.1097/01.pas.0000213330.71745.39
  13. Matsuyama A, Hisaoka M, Iwasaki M, Iwashita M, Hisanaga S, Hashimoto H. TLE1 expression in malignant mesothelioma. Virchows Arch 2010;457:577-583. https://doi.org/10.1007/s00428-010-0975-8
  14. Fraga MF, Berdasco M, Ballestar E, Ropero S, Lopez-Nieva P, Lopez-Serra L, et al. Epigenetic inactivation of the Groucho homologue gene TLE1 in hematologic malignancies. Cancer Res 2008;68:4116-4122. https://doi.org/10.1158/0008-5472.CAN-08-0085
  15. Dayyani F, Wang J, Yeh JR, Ahn EY, Tobey E, Zhang DE, et al. Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival. Blood 2008;111:4338-4347. https://doi.org/10.1182/blood-2007-07-103291
  16. Zhang L, Yang L, Liu X, Chen W, Chang L, Chen L, et al. MicroRNA-657 promotes tumorigenesis in hepatocellular carcinoma by targeting transducin-like enhancer protein 1 through nuclear factor kappa B pathways. Hepatology 2013;57:1919-1930. https://doi.org/10.1002/hep.26162
  17. Brunquell C, Biliran H, Jennings S, Ireland SK, Chen R, Ruoslahti E. TLE1 is an anoikis regulator and is downregulated by Bit1 in breast cancer cells. Mol Cancer Res 2012;10:1482-1495. https://doi.org/10.1158/1541-7786.MCR-12-0144
  18. Yao X, Ireland SK, Pham T, Temple B, Chen R, Raj MH, et al. TLE1 promotes EMT in A549 lung cancer cells through suppression of E-cadherin. Biochem Biophys Res Commun 2014;455:277-284. https://doi.org/10.1016/j.bbrc.2014.11.007
  19. Lee HW, Kim EH, Oh MH. Clinicopathologic implication of ezrin expression in non-small cell lung cancer. Korean J Pathol 2012;46:470-477. https://doi.org/10.4132/KoreanJPathol.2012.46.5.470
  20. Gasperowicz M, Otto F. Mammalian Groucho homologs: redundancy or specificity? J Cell Biochem 2005;95:670-687. https://doi.org/10.1002/jcb.20476
  21. Jan Y, Matter M, Pai JT, Chen YL, Pilch J, Komatsu M, et al. A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Cell 2004;116:751-762. https://doi.org/10.1016/S0092-8674(04)00204-1
  22. Allen T, van Tuyl M, Iyengar P, Jothy S, Post M, Tsao MS, et al. Grg1 acts as a lung-specific oncogene in a transgenic mouse model. Cancer Res 2006;66:1294-1301. https://doi.org/10.1158/0008-5472.CAN-05-1634

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