Abstract
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.



Similar content being viewed by others
References
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 11:518
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 18:956–968
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 27:159–169
Kong X, Moran MS, Zhao Y, Yang Q (2012) Inhibition of metadherin sensitizes breast cancer cells to AZD6244. Cancer Biol Ther 13:43–49
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:e29363
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 17:7539–7550
Brown DM, Ruoslahti E (2004) Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell 5:365–374
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 30:894–901
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
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 30:145–150
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 102:1151–1157
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 17:7294–7302
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
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):1051–1060
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. 20:1188–1196
Ying Z, Li J, Li M (2011) Astrocyte elevated gene 1: biological functions and molecular mechanism in cancer and beyond. Cell Biosci 1:36
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 107:18398–18403
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 468:48–57
Tsuchiya N, Nakagama H (2010) MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis. Mutat Res 693:94–100
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 174:2044–2050
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 53:1538–1548
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 286:19982–19992
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
Hu G, Wei Y, Kang Y (2009) The multifaceted role of MTDH/AEG-1 in cancer progression. Clin Cancer Res 15:5615–5620
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 130:1–8
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 7:547–548
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 21:4950–4958
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 425:411–414
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 67:9568–9576
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 81172287 and No.81200330).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Nan-Wang and Xilin-Du equally contributed to this work.
Rights and permissions
About this article
Cite this article
Wang, N., Du, X., Zang, L. et al. Prognostic impact of Metadherin–SND1 interaction in colon cancer. Mol Biol Rep 39, 10497–10504 (2012). https://doi.org/10.1007/s11033-012-1933-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-012-1933-0