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Tumor Biology

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01.12.2015 | Research Article

The clinical and prognostic significance of midkine in breast cancer patients

verfasst von: Fuguang Li, Peijun Tian, Jun Zhang, Changyuan Kou

Erschienen in: Tumor Biology | Ausgabe 12/2015

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Abstract

Midkine overexpression has been shown to be a tumor biomarker in several types of human cancer, but little is known about the clinical significance of midkine in breast cancer patients. The aim of this study was to analyze the expression of midkine in breast cancer and its correlation with clinicopathological characteristics, including breast cancer patient’s survival. The expression status of midkine in breast cancer from Gene Expression Omnibus (GEO accession number: GDS3853) was observed initially. Furthermore, the expression of midkine messenger RNA (mRNA) and protein was examined in breast cancer and normal mammary tissues through real-time PCR and immunohistochemistry. Moreover, the relationship of midkine protein expression with clinical characteristics of 170 breast cancer patients was analyzed by immunohistochemistry. In our results, midkine was up-expressed in breast cancer tissues compared with normal mammary tissues in microarray data (GDS3853). Midkine mRNA and protein expression was significantly increased in breast cancer tissues than in normal mammary tissues. By immunohistochemistry, high levels of midkine protein were positively associated with the status of clinical stage, T classification, N classification, and M classification in breast cancer patients. Furthermore, midkine overexpression was an independent poor prognostic indicator for the survival of patients with breast cancer. In conclusion, overexpression of midkine protein serves as an unfavorable prognostic biomarker in breast cancer patients.

Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015;385:977–1010.CrossRefPubMed

Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, et al. Breast cancer metastasis: challenges and opportunities. Cancer Res. 2009;69:4951–3.CrossRefPubMed

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.CrossRefPubMed

Bombonati A, Sgroi DC. The molecular pathology of breast cancer progression. J Pathol. 2011;223:307–17.CrossRefPubMed

Murasugi A, Tohma-Aiba Y. Production of native recombinant human midkine in the yeast, Pichia pastoris. Protein Expr Purif. 2003;27:244–52.CrossRefPubMed

Kadomatsu K, Muramatsu T. Midkine and pleiotrophin in neural development and cancer. Cancer Lett. 2004;204:127–43.CrossRefPubMed

Qi M, Ikematsu S, Maeda N, Ichihara-Tanaka K, Sakuma S, Noda M, et al. Haptotactic migration induced by midkine. Involvement of protein-tyrosine phosphatase zeta. Mitogen-activated protein kinase, and phosphatidylinositol 3-kinase. J Biol Chem. 2001;276:15868–75.CrossRefPubMed

Muramatsu T. Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem. 2002;132:359–71.CrossRefPubMed

Choudhuri R, Zhang HT, Donnini S, Ziche M, Bicknell R. An angiogenic role for the neurokines midkine and pleiotrophin in tumorigenesis. Cancer Res. 1997;57:1814–9.PubMed

10.

Kadomatsu K, Hagihara M, Akhter S, Fan QW, Muramatsu H, Muramatsu T. Midkine induces the transformation of NIH3T3 cells. Br J Cancer. 1997;75:354–9.CrossRefPubMedPubMedCentral

11.

Ota K, Fujimori H, Ueda M, Shiniriki S, Kudo M, Jono H, et al. Midkine as a prognostic biomarker in oral squamous cell carcinoma. Br J Cancer. 2008;99:655–62.CrossRefPubMedPubMedCentral

12.

Aridome K, Tsutsui J, Takao S, Kadomatsu K, Ozawa M, Aikou T, et al. Increased midkine gene expression in human gastrointestinal cancers. Jpn J Cancer Res. 1995;86:655–61.CrossRefPubMed

13.

Ye C, Qi M, Fan QW, Ito K, Akiyama S, Kasai Y, et al. Expression of midkine in the early stage of carcinogenesis in human colorectal cancer. Br J Cancer. 1999;79:179–84.CrossRefPubMedPubMedCentral

14.

Kato M, Shinozawa T, Kato S, Awaya A, Terada T. Increased midkine expression in hepatocellular carcinoma. Arch Pathol Lab Med. 2000;124:848–52.PubMed

15.

Kato M, Shinozawa T, Kato S, Endo K, Terada T. Increased midkine expression in intrahepatic cholangiocarcinoma: immunohistochemical and in situ hybridization analyses. Liver. 2000;20:216–21.CrossRefPubMed

16.

Ma Z, Li H, Wang B, Shen Q, Cui E, Min L, et al. Midkine mRNA level in peripheral blood mononuclear cells is a novel biomarker for primary non-small cell lung cancer: a prospective study. J Cancer Res Clin Oncol. 2013;139:557–62.CrossRefPubMed

17.

Kato M, Maeta H, Kato S, Shinozawa T, Terada T. Immunohistochemical and in situ hybridization analyses of midkine expression in thyroid papillary carcinoma. Mod Pathol. 2000;13:1060–5.CrossRefPubMed

18.

Hidaka H, Yagasaki H, Takahashi Y, Hama A, Nishio N, Tanaka M, et al. Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia. Leuk Res. 2007;31:1045–51.CrossRefPubMed

19.

Moon HS, Park WI, Sung SH, Choi EA, Chung HW, Woo BH. Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer. Gynecol Oncol. 2003;88:289–97.CrossRefPubMed

20.

Nakanishi T, Kadomatsu K, Okamoto T, Tomoda Y, Muramatsu T. Expression of midkine and pleiotropin in ovarian tumors. Obstet Gynecol. 1997;90:285–90.CrossRefPubMed

21.

Konishi N, Nakamura M, Nakaoka S, Hiasa Y, Cho M, Uemura H, et al. Immunohistochemical analysis of midkine expression in human prostate carcinoma. Oncology. 1999;57:253–7.CrossRefPubMed

22.

Luo W, Li S, Peng B, Ye Y, Deng X, Yao K. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 2013;8, e56324.CrossRefPubMedPubMedCentral

23.

Muramatsu T. Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases. Proce Jpn Acad Ser B Phys Biolog Sci. 2010;86:410–25.CrossRef

24.

Ikematsu S, Yano A, Aridome K, Kikuchi M, Kumai H, Nagano H, et al. Serum midkine levels are increased in patients with various types of carcinomas. Br J Cancer. 2000;83:701–6.CrossRefPubMedPubMedCentral

25.

Ibusuki M, Fujimori H, Yamamoto Y, Ota K, Ueda M, Shinriki S, et al. Midkine in plasma as a novel breast cancer marker. Cancer Sci. 2009;100:1735–9.CrossRefPubMed

26.

Kretschmer C, Sterner-Kock A, Siedentopf F, Schoenegg W, Schlag PM, Kemmner W. Identification of early molecular markers for breast cancer. Mol Cancer. 2011;10:15.CrossRefPubMedPubMedCentral

27.

Qin Li L, Huang HL, Ping JL, Xu W, Li J, Dai LC. Expression of midkine and endoglin in breast carcinomas with different immunohistochemical profiles. APMIS. 2011;119:103–10.CrossRefPubMed

28.

Shimada H, Nabeya Y, Tagawa M, Okazumi S, Matsubara H, Kadomatsu K, et al. Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma. Cancer Sci. 2003;94:628–32.CrossRefPubMed

29.

Zhu WW, Guo JJ, Guo L, Jia HL, Zhu M, Zhang JB, et al. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma. Clin Cancer Res. 2013;19:3944–54.CrossRefPubMed

30.

Ota K, Fujimori H, Ueda M, Jono H, Shinriki S, Ota T, et al. Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma. Int J Oncol. 2010;37:797–804.PubMed

31.

Zhao ZQ, Yang S, Lu HS. Expression of midkine and vascular endothelial growth factor in gastric cancer and the association of high levels with poor prognosis and survival. Mol Med Rep. 2012;5:415–9.PubMed

Titel: The clinical and prognostic significance of midkine in breast cancer patients
verfasst von: Fuguang Li
Peijun Tian
Jun Zhang
Changyuan Kou
Publikationsdatum: 01.12.2015
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 12/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-3710-x

Springer Medizin

The clinical and prognostic significance of midkine in breast cancer patients

Abstract

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Springer Medizin

Abstract

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