Molecular Biology Reports

, Volume 39, Issue 12, pp 10497–10504 | Cite as

Prognostic impact of Metadherin–SND1 interaction in colon cancer

  • Nan Wang
  • Xilin Du
  • Li Zang
  • Nuan Song
  • Tao Yang
  • Rui Dong
  • Tao Wu
  • Xianli HeEmail author
  • Jianguo LuEmail author


The interaction between Metadherin (MTDH) and Staphylococcal nuclease homology domain containing 1 (SND1) is involved in tumorigenesis and tumor progression of several human malignancies. However, its roles in colon cancer are still unclear. To investigate the clinical value of MTDH and SND1 expression in colon cancer. Immunohistochemical staining was performed to detect the expression of MTDH and SND1 using human colon cancer and their corresponding non-cancerous colon tissues from 196 patients’ biopsies. Positive expression of MTDH and SND1 were both increased in colon cancer tissues compared to paired non-cancerous colon tissues. There was a positive correlation between MTDH and SND1 expression in colon cancer tissues (r = 0.86, p < 0.001). In addition, their positive expression were both significantly associated with nodal status (both p = 0.02), pathological stage (p = 0.006 and 0.008, respectively) and differentiation (both p = 0.03). Moreover, the overall survival in colon cancer patients with positive expression of MTDH and SND1 were significantly shorter than those without their expression (both p = 0.01). Furthermore, multivariate Cox regression analysis suggested that positive expression of MTDH and SND1 was an independent poor prognostic predictor in colon cancer. Our data suggest that the increased expression of MTDH and/or SND1 is closely related to carcinogenesis, progression, and prognosis of colon cancer. The co-expression of MTDH/SND1 may be a novel distinctive marker to benefit us in prediction of the prognosis in colon cancer.


Metadherin Staphylococcal nuclease homology domain containing 1 Immunohistochemistry Colon cancer Prognosis 



This work was supported by the National Natural Science Foundation of China (No. 81172287 and No.81200330).


  1. 1.
    Neumann J, Bahr F, Horst D, Kriegl L, Engel J, Luque RM, Gerhard M, Kirchner T, Jung A (2011) SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer. BMC Cancer 11:518PubMedCrossRefGoogle Scholar
  2. 2.
    Beji A, Horst D, Engel J, Kirchner T, Ullrich A (2012) Toward the prognostic significance and therapeutic potential of HER3 receptor tyrosine kinase in human colon cancer. Clin Cancer Res 18:956–968PubMedCrossRefGoogle Scholar
  3. 3.
    Gulubova MV, Ananiev JR, Vlaykova TI, Yovchev Y, Tsoneva V, Manolova IM (2012) Role of dendritic cells in progression and clinical outcome of colon cancer. Int J Colorectal Dis 27:159–169PubMedCrossRefGoogle Scholar
  4. 4.
    Kong X, Moran MS, Zhao Y, Yang Q (2012) Inhibition of metadherin sensitizes breast cancer cells to AZD6244. Cancer Biol Ther 13:43–49PubMedCrossRefGoogle Scholar
  5. 5.
    Zhao Y, Kong X, Li X, Yan S, Yuan C, Hu W, Yang Q (2011) Metadherin mediates lipopolysaccharide-induced migration and invasion of breast cancer cells. PLoS ONE 6:e29363PubMedCrossRefGoogle Scholar
  6. 6.
    Hui AB, Bruce JP, Alajez NM, Shi W, Yue S, Perez-Ordonez B, Xu W, O’Sullivan B, Waldron J, Cummings B, Gullane P, Siu L, Liu FF (2011) Significance of dysregulated metadherin and microRNA-375 in head and neck cancer. Clin Cancer Res 17:7539–7550PubMedCrossRefGoogle Scholar
  7. 7.
    Brown DM, Ruoslahti E (2004) Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell 5:365–374PubMedCrossRefGoogle Scholar
  8. 8.
    Yu C, Chen K, Zheng H, Guo X, Jia W, Li M, Zeng M, Li J, Song L (2009) Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis. Carcinogenesis 30:894–901PubMedCrossRefGoogle Scholar
  9. 9.
    Zhao Y, Moran MS, Yang Q, Liu Q, Yuan C, Hong S, Kong B (2012) Metadherin regulates radioresistance in cervical cancer cells. Oncol Rep 27(5):1520–1526. doi: 10.3892/or.2012.1692 PubMedGoogle Scholar
  10. 10.
    Meng F, Luo C, Ma L, Hu Y, Lou G (2011) Clinical significance of astrocyte elevated gene-1 expression in human epithelial ovarian carcinoma. Int J Gynecol Pathol 30:145–150PubMedCrossRefGoogle Scholar
  11. 11.
    Li X, Kong X, Huo Q, Guo H, Yan S, Yuan C, Moran MS, Shao C, Yang Q (2011) Metadherin enhances the invasiveness of breast cancer cells by inducing epithelial to mesenchymal transition. Cancer Sci 102:1151–1157PubMedCrossRefGoogle Scholar
  12. 12.
    Zhu K, Dai Z, Pan Q, Wang Z, Yang GH, Yu L, Ding ZB, Shi GM, Ke AW, Yang XR, Tao ZH, Zhao YM, Qin Y, Zeng HY, Tang ZY, Fan J, Zhou J (2011) Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res 17:7294–7302PubMedCrossRefGoogle Scholar
  13. 13.
    Li C, Li Y, Wang X, Wang Z, Cai J, Wang L, Zhao Y, Song H, Meng X, Ning X, Xu C, Lin M, Li L, Geng J (2012) Elevated expression of astrocyte elevated gene-1 (AEG-1) is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III–IV serous ovarian carcinoma. Histopathology 60(6):953–963. doi: 10.1111/j.1365-2559.2012.04182.x PubMedCrossRefGoogle Scholar
  14. 14.
    Sun S, Ke Z, Wang F, Li S, Chen W, Han A, Wang Z, Shi H, Wang LT, Chen X (2011) Overexpression of astrocyte-elevated gene-1 is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through up-regulation of matrix metalloproteinase-9 expression. Hum Pathol 43(7):1051–1060PubMedCrossRefGoogle Scholar
  15. 15.
    Song H, Li C, Lu R, Zhang Y, Geng J (2010) Expression of astrocyte elevated gene-1: a novel marker of the pathogenesis, progression, and poor prognosis for endometrial cancer. Int J Gynecol Cancer. 20:1188–1196PubMedCrossRefGoogle Scholar
  16. 16.
    Ying Z, Li J, Li M (2011) Astrocyte elevated gene 1: biological functions and molecular mechanism in cancer and beyond. Cell Biosci 1:36PubMedCrossRefGoogle Scholar
  17. 17.
    Liu K, Chen C, Guo Y, Lam R, Bian C, Xu C, Zhao DY, Jin J, MacKenzie F, Pawson T, Min J (2010) Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain. Proc Natl Acad Sci USA 107:18398–18403PubMedCrossRefGoogle Scholar
  18. 18.
    Hossain MJ, Korde R, Singh PK, Kanodia S, Ranjan R, Ram G, Kalsey GS, Singh R, Malhotra P (2010) Plasmodium falciparum Tudor Staphylococcal Nuclease interacting proteins suggest its role in nuclear as well as splicing processes. Gene 468:48–57PubMedCrossRefGoogle Scholar
  19. 19.
    Tsuchiya N, Nakagama H (2010) MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis. Mutat Res 693:94–100PubMedCrossRefGoogle Scholar
  20. 20.
    Kuruma H, Kamata Y, Takahashi H, Igarashi K, Kimura T, Miki K, Miki J, Sasaki H, Hayashi N, Egawa S (2009) Staphylococcal nuclease domain-containing protein 1 as a potential tissue marker for prostate cancer. Am J Pathol 174:2044–2050PubMedCrossRefGoogle Scholar
  21. 21.
    Yoo BK, Santhekadur PK, Gredler R, Chen D, Emdad L, Bhutia S, Pannell L, Fisher PB, Sarkar D (2011) Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma. Hepatology 53:1538–1548PubMedCrossRefGoogle Scholar
  22. 22.
    Blanco MA, Aleckovi M, Hua Y, Li T, Wei Y, Xu Z, Cristea IM, Kang Y (2011) Identification of staphylococcal nuclease domain-containing 1 (SND1) as a Metadherin-interacting protein with metastasis-promoting functions. J Biol Chem 286:19982–19992PubMedCrossRefGoogle Scholar
  23. 23.
    Liu DC, Yang ZL (2011) MTDH and EphA7 are markers for metastasis and poor prognosis of gallbladder adenocarcinoma. Diagn Cytopathol. doi: 10.1002/dc.21821 Google Scholar
  24. 24.
    Hu G, Wei Y, Kang Y (2009) The multifaceted role of MTDH/AEG-1 in cancer progression. Clin Cancer Res 15:5615–5620PubMedCrossRefGoogle Scholar
  25. 25.
    Yoo BK, Emdad L, Lee SG, Su ZZ, Santhekadur P, Chen D, Gredler R, Fisher PB, Sarkar D (2011) Astrocyte elevated gene-1 (AEG-1): a multifunctional regulator of normal and abnormal physiology. Pharmacol Ther 130:1–8PubMedCrossRefGoogle Scholar
  26. 26.
    Bhutia SK, Kegelman TP, Das SK, Azab B, Su ZZ, Lee SG, Sarkar D, Fisher PB (2011) Astrocyte elevated gene-1 activates AMPK in response to cellular metabolic stress and promotes protective autophagy. Autophagy 7:547–548PubMedCrossRefGoogle Scholar
  27. 27.
    Yang J, Aittomaki S, Pesu M, Carter K, Saarinen J, Kalkkinen N, Kieff E, Silvennoinen O (2002) Identification of p100 as a coactivator for STAT6 that bridges STAT6 with RNA polymerase II. EMBO J 21:4950–4958PubMedCrossRefGoogle Scholar
  28. 28.
    Caudy AA, Ketting RF, Hammond SM, Denli AM, Bathoorn AM, Tops BB, Silva JM, Myers MM, Hannon GJ, Plasterk RH (2003) A micrococcal nuclease homologue in RNAi effector complexes. Nature 425:411–414PubMedCrossRefGoogle Scholar
  29. 29.
    Tsuchiya N, Ochiai M, Nakashima K, Ubagai T, Sugimura T, Nakagama H (2007) SND1, a component of RNA-induced silencing complex, is up-regulated in human colon cancers and implicated in early stage colon carcinogenesis. Cancer Res 67:9568–9576PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of General Surgery, Tangdu HospitalFourth Military Medical UniversityXi’anPeople’s Republic of China

Personalised recommendations