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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

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Abstract

Purpose

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

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

S100A10:

S100 Calcium-binding protein A10

iTRAQ:

Isobaric tags for relative and absolute quantification

FAP:

Familial adenomatous polyposis

CRC:

Colorectal cancers

APC:

Adenomatous polyposis coli

DMH:

1,2-Dimethylhydrazine

H&E:

Hematoxylin and eosin

IHC:

Immunohistochemical

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Funding

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).

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Correspondence to S. Zhang.

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The authors declare no conflict of interest.

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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.

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

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Liu, G., Fei, F., Qu, J. et al. 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. Clin Transl Oncol 21, 220–231 (2019). https://doi.org/10.1007/s12094-018-1912-6

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