Neogenin expression is inversely associated with breast cancer grade in ex vivo

World Journal of Surgical Oncology

Zheli Xu²  Rangjuan Cao¹  Qiang Li¹  Wanying Xing² 

[1] Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China;Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China

关键词: predictive biomarkers;    histological grading;    breast cancer;    Neogenin;   

Others  :  1147251
DOI  :  10.1186/1477-7819-12-352

 received in 2014-05-29, accepted in 2014-10-02,  发布年份 2014

【 摘 要 】

Background

Neogenin is closely related to the human tumor suppressor gene deleted in colorectal cancer and plays a role in mammary morphogenesis. This study aimed to assess neogenin expression in breast cancer for any clinically significant association.

Methods

A total of 54 breast cancer patients who underwent modified radical mastectomy were enrolled for immunohistochemical and quantitative real-time PCR analysis of neogenin expression in their cancerous breast tissues in comparison to matching distant non-cancerous tissues.

Results

The data showed that the neogenin protein was either strongly or moderately expressed in the cytoplasm of the distant non-cancerous cells. In contrast, neogenin protein was either weakly or not expressed in the cytoplasm of 51/54 (94.4%) breast cancer cells, among which 13 breast cancer cases did not express neogenin protein at all (13/54, 24.1%). Similarly, levels of neogenin mRNA were significantly lower in breast cancer tissues than that of the matched distant non-cancerous tissues (51/54, 94.4%). Neogenin expression was inversely associated with breast cancer grade; that is, grade III breast cancer expressed much less neogenin than grade I-II (P < 0.05).

Conclusions

This study indicates that neogenin expression in breast cancer tissues is inversely associated with tumor grade.

【 授权许可】

   
2014 Xing et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Dey S, Soliman AS: Cancer in the global health era: opportunities for the Middle East and Asia. Asia Pac J Public Health 2010, 22:75S-82S.
• [2]Wang YC, Wei LJ, Liu JT, Li SX, Wang QS: Comparison of cancer incidence between China and the USA. Cancer Biol Med 2012, 9:128-132.
• [3]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225-249.
• [4]La Vecchia C, Bosetti C, Lucchini F, Bertuccio P, Negri E, Boyle P, Levi F: Cancer mortality in Europe, 2000–2004, and an overview of trends since 1975. Ann Oncol 2010, 21:1323-1360.
• [5]Chung C, Christianson M: Predictive and prognostic biomarkers with therapeutic targets in breast, colorectal, and non-small cell lung cancers: a systemic review of current development, evidence, and recommendation. J Oncol Pharm Pract 2014, 20:11-28.
• [6]Pathmanathan N, Balleine RL: Ki67 and proliferation in breast cancer. J Clin Pathol 2013, 66:512-516.
• [7]Harvey JM, Clark GM, Osborne CK, Allred DC: Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999, 17:1474-1481.
• [8]Mohsin SK, Weiss H, Havighurst T, Clark GM, Berardo M, Roanh le D, To TV, Qian Z, Love RR, Allred DC: Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 2004, 17:1545-1554.
• [9]Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, Buyse M, Baum M, Buzdar A, Colleoni M: Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 2010, 28:509-518.
• [10]Ross JS, Linette GP, Stec J, Clark E, Ayers M, Leschly N, Symmans WF, Hortobagyi GN, Pusztai L: Breast cancer biomarkers and molecular medicine: part II. Expert Rev Mol Diagn 2004, 4:169-188.
• [11]Allred DC: Issues and updates: evaluating estrogen receptor-α, progesterone receptor, and HER2 in breast cancer. Modern Pathology 2010, 23:S52-S59.
• [12]Stagg J, Allard B: Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects. Ther Adv Med Oncol 2013, 5:169-181.
• [13]Meyerhardt JA, Look AT, Bigner SH, Fearon ER: Identification and characterization of neogenin, a DCC-related gene. Oncogene 1997, 14:1129-1136.
• [14]Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller BK, Strittmatter SM: Neogenin mediates the action of repulsive guidance molecule. Nat Cell Biol 2004, 6:756-762.
• [15]Matsunaga E, Tauszig-Delamasure S, Monnier PP, Mueller BK, Strittmatter SM, Mehlen P, Chédotal A: RGM and its receptor neogenin regulate neuronal survival. Nat Cell Biol 2004, 6:749-755.
• [16]De Vries M, Cooper HM: Emerging roles for neogenin and its ligands in CNS development. J Neurochem 2008, 106:1483-1492.
• [17]Hebrok M, Reichardt LF: Brain meets pancreas: netrin, an axon guidance molecule, controls epithelial cell migration. Trends Cell Biol 2004, 14:153-155.
• [18]Liu Y, Stein E, Oliver T, Li Y, Brunken WJ, Koch M, Tessier-Lavigne M, Hogan BLM: Novel role for netrins in regulating epithelial behavior during lung branching morphogenesis. Curr Biol 2004, 14:897-905.
• [19]Lu X, Le Noble F, Yuan L, Jiang Q, De Lafarge B, Sugiyama D, Bréant C, Claes F, De Smet F, Thomas J-L: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 2004, 432:179-186.
• [20]Arakawa H: Netrin-1 and its receptors in tumorigenesis. Nat Rev Cancer 2004, 4:978-987.
• [21]Fitamant J, Guenebeaud C, Coissieux M-M, Guix C, Treilleux I, Scoazec J-Y, Bachelot T, Bernet A, Mehlen P: Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer. PNAS 2008, 105:4850-4855.
• [22]Ly NP, Komatsuzaki K, Fraser IP, Tseng AA, Prodhan P, Moore KJ, Kinane TB: Netrin-1 inhibits leukocyte migration in vitro and in vivo. Science Signaling 2005, 102:14729.
• [23]Lee JE, Kim HJ, Bae JY, Kim SW, Park J-S, Shin HJ, Han W, Kim S-W, Kang K-S, Noh D-Y: Neogenin expression may be inversely correlated to the tumorigenicity of human breast cancer. BMC Cancer 2005, 5:154. BioMed Central Full Text
• [24]Benson JR, Weaver DL, Mittra I, Hayashi M: The TNM staging system and breast cancer. Lancet Oncol 2003, 4:56-60.
• [25]Frank GA, Danilova NV, Andreeva I, Nefedova NA: [WHO classification of tumors of the breast, 2012]. Arkh Patol 2013, 75:53-63.
• [26]Wu X, Li Y, Wan X, Kayira TM, Cao R, Ju X, Zhu X, Zhao G: Down-regulation of neogenin accelerated glioma progression through promoter methylation and its overexpression in SHG-44 induced apoptosis. PLoS One 2012, 7:e38074.
• [27]Li VS, Yuen ST, Chan TL, Yan HH, Law WL, Yeung BH, Chan AS, Tsui WY, So S, Chen X, Leung SY: Frequent inactivation of axon guidance molecule RGMA in human colon cancer through genetic and epigenetic mechanisms. Gastroenterology 2009, 137:176-187.
• [28]Latil A, Chene L, Cochant-Priollet B, Mangin P, Fournier G, Berthon P, Cussenot O: Quantification of expression of netrins, slits and their receptors in human prostate tumors. Int J Cancer 2003, 103:306-315.
• [29]Bondy ML, Scheurer ME, Malmer B, Barnholtz‒Sloan JS, Davis FG, Il'Yasova D, Kruchko C, McCarthy BJ, Rajaraman P, Schwartzbaum JA: Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium. Cancer 2008, 113:1953-1968.
• [30]Lavelle K, Moran A, Howell A, Bundred N, Campbell M, Todd C: Older women with operable breast cancer are less likely to have surgery. Br J Surg 2007, 94:1209-1215.
• [31]Bernet A, Mehlen P: Dependence receptors: when apoptosis controls tumor progression. Bull Cancer 2007, 94:10012-10017.
• [32]Strizzi L, Bianco C, Raafat A, Abdallah W, Chang C, Raafat D, Hirota M, Hamada S, Sun Y, Normanno N, Callahan R, Hinck L, Salomon D: Netrin-1 regulates invasion and migration of mouse mammary epithelial cells overexpressing Cripto-1 in vitro and in vivo. J Cell Sci 2005, 118(Pt 20):4633-43.