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Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma

  • Authors:
    • Lemeng Chao
    • Jianfeng Liu
    • Dewei Zhao
  • View Affiliations / Copyright

    Affiliations: Graduate College, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Orthopaedics, Affiliated Zhongshan Hospital, Dalian University, Dalian, Liaoning 116001, P.R. China
    Copyright: © Chao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2891-2896
    |
    Published online on: March 6, 2017
       https://doi.org/10.3892/ol.2017.5803
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Abstract

Sine oculis homeobox homolog 1 (Six1) is an evolutionarily conserved transcription factor that acts as master regulator of development and is frequently dysregulated in various types of cancer. Six1 has been demonstrated to be upregulated in human osteosarcoma cell lines compared with osteoblastic cell lines. However, the association of Six1 expression with the progression and prognosis of osteosarcoma patients remains unclear. The purpose of the present study was to investigate the association between Six1 expression and the clinicopathological characteristics and prognosis of osteosarcoma. Six1 protein was detected by immunohistochemistry in a series of 100 osteosarcoma patients, and Kaplan-Meier survival analysis was performed to assess prognosis. The results revealed that increased Six1 protein expression was prevalent in osteosarcoma and was significantly associated with Enneking stage (P=0.002) and tumor size (P=0.010). Additionally, according to the log‑rank test and Cox regression model, expression of Six1 is indicated to be an independent prognostic factor in osteosarcoma patients. In summary, positive expression of Six1 protein is closely associated with the tumor progression and poor survival of osteosarcoma patients. The results suggest that Six1 is a overexpressed in individuals with poor prognosis, and may thus be used as a prognostic biomarker in patients with osteosarcoma.
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1 

Marina N, Gebhardt M, Teot L and Gorlick R: Biology and therapeutic advances for pediatric osteosarcoma. Oncologist. 9:422–441. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Fagioli F, Biasin E, Mereuta OM, Muraro M, Luksch R, Ferrari S, Aglietta M and Madon E: Poor prognosis osteosarcoma: New therapeutic approach. Bone Marrow Transplant. 41:(Suppl 2). S131–S134. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Fletcher CDM, Unni KK and Mertens F: Conventional osteosarcomaWorld Health Organization Classification of Tumours - Pathology and Genetics of Tumors of Soft Tissue and Bone. 4th. IARC Press; Lyon: pp. 192013

4 

Chou AJ and Gorlick R: Chemotherapy resistance in osteosarcoma: Current challenges and future directions. Expert Rev Anticancer Ther. 6:1075–1085. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Yao C, Wei JJ, Wang ZY, Ding HM, Li D, Yan SC, Yang YJ and Gu ZP: Perifosine induces cell apoptosis in human osteosarcoma cells: New implication for osteosarcoma therapy? Cell Biochem Biophys. 65:217–227. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Poletajew S, Fus L and Wasiutyński A: Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors. Ortop Traumatol Rehabil. 13:537–545. 2011.(In English, Polish). View Article : Google Scholar : PubMed/NCBI

7 

Hu F, Wang W, Zhou HC and Shang XF: High expression of periostin is dramatically associated with metastatic potential and poor prognosis of patients with osteosarcoma. World J Surg Oncol. 12:2872014. View Article : Google Scholar : PubMed/NCBI

8 

Nada OH, Ahmed NS and Gabal Abou HH: Prognostic significance of HLA EMR8-5 immunohistochemically analyzed expression in osteosarcoma. Diagn Pathol. 9:722014. View Article : Google Scholar : PubMed/NCBI

9 

Kumar JP: The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease. Cell Mol Life Sci. 66:565–583. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Anderson AM, Weasner BM, Weasner BP and Kumar JP: Dual transcriptional activities of SIX proteins define their roles in normal and ectopic eye development. Development. 139:991–1000. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Xu PX, Zheng W, Huang L, Maire P, Laclef C and Silvius D: Six1 is required for the early organogenesis of mammalian kidney. Development. 130:3085–3094. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Laclef C, Souil E, Demignon J and Maire P: Thymus, kidney and craniofacial abnormalities in Six 1 deficient mice. Mech Dev. 120:669–679. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Konishi Y, Ikeda K, Iwakura Y and Kawakami K: Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis. Brain Res. 1116:93–102. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Reichenberger KJ, Coletta RD, Schulte AP, Varella-Garcia M and Ford HL: Gene amplification is a mechanism of Six1 overexpression in breast cancer. Cancer Res. 65:2668–2675. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Behbakht K, Qamar L, Aldridge CS, Coletta RD, Davidson SA, Thorburn A and Ford HL: Six1 overexpression in ovarian carcinoma causes resistance to TRAIL-mediated apoptosis and is associated with poor survival. Cancer Res. 67:3036–3042. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Imam JS, Buddavarapu K, Lee-Chang JS, Ganapathy S, Camosy C, Chen Y and Rao MK: MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers. Oncogene. 29:4971–4979. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Tan J, Zhang C and Qian J: Expression and significance of Six1 and Ezrin in cervical cancer tissue. Tumour Biol. 32:1241–1247. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Zheng XH, Liang PH, Guo JX, Zheng YR, Han J, Yu LL, Zhou YG and Li L: Expression and clinical implications of homeobox gene Six1 in cervical cancer cell lines and cervical epithelial tissues. Int J Gynecol Cancer. 20:1587–1592. 2010.PubMed/NCBI

19 

Li CM, Guo M, Borczuk A, Powell CA, Wei M, Thaker HM, Friedman R, Klein U and Tycko B: Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am J Pathol. 160:2181–2190. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Yu Y, Khan J, Khanna C, Helman L, Meltzer PS and Merlino G: Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat Med. 10:175–181. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Ng KT, Man K, Sun CK, Lee TK, Poon RT, Lo CM and Fan ST: Clinicopathological significance of homeoprotein Six1 in hepatocellular carcinoma. Br J Cancer. 95:1050–1055. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Coletta RD, Christensen K, Reichenberger KJ, Lamb J, Micomonaco D, Huang L, Wolf DM, Müller-Tidow C, Golub TR, Kawakami K and Ford HL: The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1. Proc Natl Acad Sci USA. 101:6478–6483. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Coletta RD, Christensen KL, Micalizzi DS, Jedlicka P, Varella-Garcia M and Ford HL: Six1 overexpression in mammary cells induces genomic instability and is sufficient for malignant transformation. Cancer Res. 68:2204–2213. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Kundu ZS: Classification, imaging, biopsy and staging of osteosarcoma. Indian J Orthop. 48:328–346. 2014. View Article : Google Scholar

25 

Zheng W, Huang L, Wei ZB, Silvius D, Tang B and Xu PX: The role of Six1 in mammalian auditory system development. Development. 130:3989–4000. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Ikeda K, Kageyama R, Suzuki Y and Kawakami K: Six1 is indispensable for production of functional progenitor cells during olfactory epithelial development. Int J Dev Biol. 54:1453–1464. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Ford HL, Kabingu EN, Bump EA, Mutter GL and Pardee AB: Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: A possible mechanism of breast carcinogenesis. Proc Natl Acad Sci USA. 95:12608–12613. 1998. View Article : Google Scholar : PubMed/NCBI

28 

Khan J, Bittner ML, Saal LH, Teichmann U, Azorsa DO, Gooden GC, Pavan WJ, Trent JM and Meltzer PS: cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. Proc Natl Acad Sci USA. 96:13264–13269. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Yu Y, Davicioni E, Triche TJ and Merlino G: The homeoprotein six1 transcriptionally activates multiple protumorigenic genes but requires ezrin to promote metastasis. Cancer Res. 66:1982–1989. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Ozaki H, Nakamura K, Funahashi J, Ikeda K, Yamada G, Tokano H, Okamura HO, Kitamura K, Muto S, Kotaki H, et al: Six1 controls patterning of the mouse otic vesicle. Development. 131:551–562. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK, Nigam SK, Aggarwal AK, Maas R, Rose DW and Rosenfeld MG: Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature. 426:247–254. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Grifone R, Demignon J, Houbron C, Souil E, Niro C, Seller MJ, Hamard G and Maire P: Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo. Development. 132:2235–2249. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Ikeda K, Ookawara S, Sato S, Ando Z, Kageyama R and Kawakami K: Six1 is essential for early neurogenesis in the development of olfactory epithelium. Dev Biol. 311:53–68. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Micalizzi DS, Christensen KL, Jedlicka P, Coletta RD, Barón AE, Harrell JC, Horwitz KB, Billheimer D, Heichman KA, Welm AL, et al: The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling. J Clin Invest. 119:2678–2690. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Micalizzi DS, Wang CA, Farabaugh SM, Schiemann WP and Ford HL: Homeoprotein Six1 increases TGF-beta type I receptor and converts TGF-beta signaling from suppressive to supportive for tumor growth. Cancer Res. 70:10371–10380. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Liu D, Li L, Zhang XX, Wan DY, Xi BX, Hu Z, Ding WC, Zhu D, Wang XL, Wang W, et al: SIX1 promotes tumor lymphangiogenesis by coordinating TGFβ signals that increase expression of VEGF-C. Cancer Res. 74:5597–5607. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Li Z, Tian T, Lv F, Chang Y, Wang X, Zhang L, Li X, Li L, Ma W, Wu J and Zhang M: Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression. PLoS One. 8:e592032013. View Article : Google Scholar : PubMed/NCBI

38 

Jin H, Cui M, Kong J, Cui X, Lin Z, Wu Q and Liu S: Sineoculis homeobox homolog 1 protein is associated with breast cancer progression and survival outcome. Exp Mol Pathol. 97:247–252. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Hua L, Fan L, Aichun W, Yongjin Z, Qingqing C and Xiaojian W: Inhibition of Six1 promotes apoptosis, suppresses proliferation, and migration of osteosarcoma cells. Tumour Biol. 35:1925–1931. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chao L, Liu J and Zhao D: Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma. Oncol Lett 13: 2891-2896, 2017.
APA
Chao, L., Liu, J., & Zhao, D. (2017). Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma. Oncology Letters, 13, 2891-2896. https://doi.org/10.3892/ol.2017.5803
MLA
Chao, L., Liu, J., Zhao, D."Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma". Oncology Letters 13.5 (2017): 2891-2896.
Chicago
Chao, L., Liu, J., Zhao, D."Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma". Oncology Letters 13, no. 5 (2017): 2891-2896. https://doi.org/10.3892/ol.2017.5803
Copy and paste a formatted citation
x
Spandidos Publications style
Chao L, Liu J and Zhao D: Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma. Oncol Lett 13: 2891-2896, 2017.
APA
Chao, L., Liu, J., & Zhao, D. (2017). Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma. Oncology Letters, 13, 2891-2896. https://doi.org/10.3892/ol.2017.5803
MLA
Chao, L., Liu, J., Zhao, D."Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma". Oncology Letters 13.5 (2017): 2891-2896.
Chicago
Chao, L., Liu, J., Zhao, D."Increased Six1 expression is associated with poor prognosis in patients with osteosarcoma". Oncology Letters 13, no. 5 (2017): 2891-2896. https://doi.org/10.3892/ol.2017.5803
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