Clinical and Translational Oncology

, Volume 21, Issue 2, pp 220–231 | Cite as

iTRAQ-based proteomic analysis of DMH-induced colorectal cancer in mice reveals the expressions of β-catenin, decorin, septin-7, and S100A10 expression in 53 cases of human hereditary polyposis colorectal cancer

  • G. Liu
  • F. Fei
  • J. Qu
  • X. Wang
  • Y. Zhao
  • Y. Li
  • S. ZhangEmail author
Research Article



The aim of this study is to explore the roles of β-catenin, decorin, septin-7, and S100A10 expression in colorectal cancer development.


Twenty-five BALB/c mice were divided into five groups; four groups were administrated N,N-dimethylhydrazine for 0, 10, 15, and 20 weeks, and one group was administrated normal saline for 20 weeks. The colons were collected for histopathological analysis. Protein samples prepared from the frozen colon tissues of mice treated with N,N-dimethylhydrazine for the different time points were evaluated using the isobaric tags for relative and absolute quantification (iTRAQ) labeling technique coupled with the 2D liquid chromatography–tandem mass spectrometry analysis. Based on the proteomic analysis results, immunohistochemical staining of β-catenin, decorin, septin-7, and S100A10 was performed in paraffin-embedded mice colorectal tissue, and 53 cases of human hereditary polyposis colorectal cancer samples.


Colorectal cancer was observed in mice treated with N,N-dimethylhydrazine for 20 weeks, and adenomas were observed in mice subjected to the 10-, and 15-week treatments. Seventy-two differentially expressed proteins were involved in the development of cancer as per the iTRAQ and spectrometry analysis. In normal epithelium, adenoma, and cancer from human hereditary polyposis colorectal cancer, S100A10 expression (c2 = 100.989, P = 0.000) was highest in cancer, whereas decorin (c2 = 12.852, P = 0.002) and septin-7 (c2 = 66.519, P = 0.002) expressions were highest in the normal epithelium, which was confirmed via immunohistochemical staining.


The subcellular localization of β-catenin and decorin, septin-7, and S100A10 expressions are associated with the development of colorectal cancer in mice after N,N-dimethylhydrazine treatment and in human hereditary polyposis colorectal cancers.


Colorectal cancer N,N-dimethylhydrazine Hereditary polyposis colorectal cancer Differentially expressed proteins 



S100 Calcium-binding protein A10


Isobaric tags for relative and absolute quantification


Familial adenomatous polyposis


Colorectal cancers


Adenomatous polyposis coli




Hematoxylin and eosin





This work was supported in part by Grants from the National Science Foundation of China (#81472729 and #81672426), the foundation of Tianjin Health Bureau (15KG112) and the foundation of committee on science and technology of Tianjin (17ZXMFSY00120), and foundation of Tianjin Union Medical Center (2016YJ025).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethics approval

This study has been approved by Tianjin Union Medical Center’s ethics committee and has been performed according to the ethical standards laid down in the 1964 Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12094_2018_1912_MOESM1_ESM.doc (27 kb)
Supplementary material 1 (DOC 27 kb)


  1. 1.
    Kastrinos F, Mukherjee B, Tayob N, Wang F, Sparr J, Raymond VM, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009;302(16):1790–5. Scholar
  2. 2.
    Miladi-Abdennadher I, Amouri A, Ayadi L, Khabir A, Ellouze S, Tahri N, et al. A novel pathogenic germline mutation in the adenomatous polyposis coli gene in a Tunisian family with FAP. Fam Cancer. 2011;10(3):567–71. Scholar
  3. 3.
    Song G, Yuan Y, Zheng F, Yang N, et al. Novel insertion mutation p.Asp610GlyfsX23 in APC gene causes familial adenomatous polyposis in Chinese families. Gene. 2013;516(2):204–8. Scholar
  4. 4.
    Soravia C, Berk T, Madlensky L, Mitri A, Cheng H, Gallinger S, et al. Genotype-phenotype correlations in attenuated adenomatous polyposis coli. Am J Hum Genet. 1998;62(6):1290–301. Scholar
  5. 5.
    Zhang D, Fei F, Li S, Zhao Y, Yang Z, Qu J, et al. The role of beta-catenin in the initiation and metastasis of TA2 mice spontaneous breast cancer. J Cancer. 2017;8(11):2114–23. Scholar
  6. 6.
    Zhang Z, Liang S, Huang H, Wang D, Zhang X, Wu J, et al. A novel pathogenic large germline deletion in adenomatous polyposis coli gene in a Chinese family with familial adenomatous polyposis. Oncotarget. 2016;7(31):50392–400. Scholar
  7. 7.
    Svitina H, Kyryk V, Skrypkina I, Kuchma M, Bukreieva T, Areshkov P, et al. Placenta-derived multipotent cells have no effect on the size and number of DMH-induced colon tumors in rats. Exp Ther Med. 2017;14(3):2135–47. Scholar
  8. 8.
    Bekusova VV, Patsanovskii VM, Nozdrachev AD, Trashkov AP, Artemenko MR, Anisimov VN. Metformin prevents hormonal and metabolic disturbances and 1,2-dimethylhydrazine-induced colon carcinogenesis in non-diabetic rats. Cancer Biol Med. 2017;14(1):100–7. Scholar
  9. 9.
    Kuznietsova HM, Luzhenetska VK, Kotlyar IP, Rybalchenko VK. Effects of 5-Amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one intake on digestive system in a rat model of colon cancer. Sci World J. 2015;2015:376576. Scholar
  10. 10.
    Zhang S, Li M, Zhang D, Xu S, Wang X, Liu Z, et al. Hypoxia influences linearly patterned programmed cell necrosis and tumor blood supply patterns formation in melanoma. Lab Investig J Tech Methods Pathol. 2009;89(5):575–86. Scholar
  11. 11.
    Zhang S, Mercado-Uribe I, Xing Z, Sun B, Kuang J, Liu J. Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. Oncogene. 2014;33(1):116–28. Scholar
  12. 12.
    Sun B, Zhang D, Zhang S, Zhang W, Guo H, Zhao X. Hypoxia influences vasculogenic mimicry channel formation and tumor invasion-related protein expression in melanoma. Cancer Lett. 2007;249(2):188–97. Scholar
  13. 13.
    Zhang S, Mercado-Uribe I, Liu J. Tumor stroma and differentiated cancer cells can be originated directly from polyploid giant cancer cells induced by paclitaxel. Int J Cancer. 2014;134(3):508–18. Scholar
  14. 14.
    Jia L, Zhang S, Ye Y, Li X, Mercado-Uribe I, Bast RC Jr, et al. Paclitaxel inhibits ovarian tumor growth by inducing epithelial cancer cells to benign fibroblast-like cells. Cancer Lett. 2012;326(2):176–82. Scholar
  15. 15.
    Sun B, Zhang S, Zhang D, Li Y, Zhao X, Luo Y, et al. Identification of metastasis-related proteins and their clinical relevance to triple-negative human breast cancer. Clin Cancer Res. 2008;14(21):7050–9. Scholar
  16. 16.
    Migliore L, Migheli F, Spisni R, Coppede F. Genetics, cytogenetics, and epigenetics of colorectal cancer. J Biomed Biotechnol. 2011;2011:792362. Scholar
  17. 17.
    Katono K, Sato Y, Jiang SX, Kobayashi M, Saito K, Nagashio R, et al. Clinicopathological significance of S100A10 expression in lung adenocarcinomas. Asian Pacific J Cancer Prev APJCP. 2016;17(1):289–94.CrossRefGoogle Scholar
  18. 18.
    Hou Y, Yang L, Mou M, Hou Y, Zhang A, Pan N, et al. Annexin A2 regulates the levels of plasmin, S100A10 and Fascin in L5178Y cells. Cancer Investig. 2008;26(8):809–15. Scholar
  19. 19.
    Phipps KD, Surette AP, O’Connell PA, Waisman DM. Plasminogen receptor S100A10 is essential for the migration of tumor-promoting macrophages into tumor sites. Can Res. 2011;71(21):6676–83. Scholar
  20. 20.
    Tan Y, Ma SY, Wang FQ, Meng HP, Mei C, Liu A, et al. Proteomic-based analysis for identification of potential serum biomarkers in gallbladder cancer. Oncol Rep. 2011;26(4):853–9. Scholar
  21. 21.
    Ito Y, Arai K, Nozawa R, Yoshida H, Higashiyama T, Takamura Y, et al. S100A10 expression in thyroid neoplasms originating from the follicular epithelium: contribution to the aggressive characteristic of anaplastic carcinoma. Anticancer Res. 2007;27(4C):2679–83.Google Scholar
  22. 22.
    Mostowy S, Cossart P. Septins: the fourth component of the cytoskeleton. Nat Rev Mol Cell Biol. 2012;13(3):183–94. Scholar
  23. 23.
    Kinoshita A, Noda M, Kinoshita M. Differential localization of septins in the mouse brain. J Comp Neurol. 2000;428(2):223–39.CrossRefGoogle Scholar
  24. 24.
    Ihara M, Kinoshita A, Yamada S, Tanaka H, Tanigaki A, Kitano A, et al. Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa. Dev Cell. 2005;8(3):343–52. Scholar
  25. 25.
    Jia ZF, Huang Q, Kang CS, Yang WD, Wang GX, Yu SZ, et al. Overexpression of septin 7 suppresses glioma cell growth. J Neurooncol. 2010;98(3):329–40. Scholar
  26. 26.
    Igci YZ, Arslan A, Akarsu E, Erkilic S, Igci M, Oztuzcu S, et al. Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma. Endocr Pathol. 2011;22(2):86–96. Scholar
  27. 27.
    Igci YZ, Erkilic S, Arslan A. Septin 7 immunoexpression in papillary thyroid carcinoma: a preliminary study. Pathol Res Pract. 2014;210(7):426–31. Scholar
  28. 28.
    Yoon AR, Hong J, Yun CO. Adenovirus-mediated decorin expression induces cancer cell death through activation of p53 and mitochondrial apoptosis. Oncotarget. 2017;8(44):76666–85. Scholar
  29. 29.
    Bostrom P, Sainio A, Eigeliene N, Jokilammi A, Elenius K, Koskivuo I, et al. Human metaplastic breast carcinoma and decorin. Cancer Microenviron. 2017. Scholar
  30. 30.
    Neill T, Schaefer L, Iozzo RV. Decorin as a multivalent therapeutic agent against cancer. Adv Drug Deliv Rev. 2016;97:174–85. Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of PathologyTianjin Union Medical CenterTianjinPeople’s Republic of China
  2. 2.Nankai University School of MedicineNankai UniversityTianjinPeople’s Republic of China
  3. 3.Graduate SchoolTianjin University of Traditional Chinese MedicineTianjinPeople’s Republic of China
  4. 4.Department of General SurgeryTianjin Union Medical CenterTianjinPeople’s Republic of China
  5. 5.Departments of Colorectal SurgeryTianjin Union Medical CenterTianjinPeople’s Republic of China

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