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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

MiR-155, a potential serum marker of extramammary Paget’s disease

Authors: Hao Guo, Rui-Qun Qi, Jie Sheng, Chang Liu, Hang Ma, He-Xiao Wang, Jiu-Hong Li, Xing-Hua Gao, Yin-Sheng Wan, Hong-Duo Chen

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Extramammary Paget’s disease (EMPD), a rare skin malignancy with non-specific manifestations, is often misdiagnosed as eczema of scrotum or tinea cruris. Although the diagnosis of EMPD could be confirmed by biopsy, it can be delayed as patients are reluctant to receive invasive operations. Herein, we investigated the serum miRNA expressions of EMPD patients and compared to that of the eczema of scrotum or tinea cruris patients as well as health volunteers for potential diagnostic markers for EMPD.

Methods

Altogether 45 subjects including 16 patients diagnosed with EMPD, 12 patients diagnosed with eczema of scrotum or tinea cruris and 17 healthy volunteers were enrolled in this study. Serum from all of subjects were collected to identify miRNAs (by miRNA array global normalization, RT-PCR validation, and receiver operating characteristic curve analysis) that could be potential diagnostic markers for EMPD.

Results

The miRNA array analyses revealed that the expressions of 37 miRNAs from the EMPD patients were different (change ≥4-fold) from health volunteers. Among these miRNAs, the expression of miR-155 was significantly increased (p < 0.01) in the EMPD patients as compared with that of the health volunteers and the eczema of scrotum or the tinea cruris patients (no difference between these two control groups). In addition, receiver operating characteristic (ROC) curve analysis showed that diagnostic capacities (defined as the area under curve of ROC) of miR-155 are 0.85 (as compared with health volunteers group) and 0.81 (as compared with the eczema of scrotum or the tinea cruris patients group), respectively.

Conclusion

The serum miRNA expression of gene miR-155 in the EMPD patients was differentiated from that of other subjects warranting further validation of miR-155 as a diagnostic marker of EMPD.
Literature
1.
go back to reference Wagner G, Sachse MM. Extramammary Paget disease - clinical appearance, pathogenesis, management. J Dtsch Dermatol Ges. 2011;9:448–54.PubMed Wagner G, Sachse MM. Extramammary Paget disease - clinical appearance, pathogenesis, management. J Dtsch Dermatol Ges. 2011;9:448–54.PubMed
2.
go back to reference Lam C, Funaro D. Extramammary Paget's disease: summary of current knowledge. Dermatol Clin. 2010;28:807–26.CrossRef Lam C, Funaro D. Extramammary Paget's disease: summary of current knowledge. Dermatol Clin. 2010;28:807–26.CrossRef
3.
go back to reference Padrnos L, Karlin N, Halfdanarson TR. Mayo Clinic Cancer center experience of metastatic Extramammary Paget disease 1998-2012. Rare Tumors. 2016;8:6804.CrossRef Padrnos L, Karlin N, Halfdanarson TR. Mayo Clinic Cancer center experience of metastatic Extramammary Paget disease 1998-2012. Rare Tumors. 2016;8:6804.CrossRef
4.
go back to reference Hatta N, Yamada M, Hirano T, Fujimoto A, Morita R. Extramammary Paget's disease: treatment, prognostic factors and outcome in 76 patients. Br J Dermatol. 2008;158:313–8.PubMed Hatta N, Yamada M, Hirano T, Fujimoto A, Morita R. Extramammary Paget's disease: treatment, prognostic factors and outcome in 76 patients. Br J Dermatol. 2008;158:313–8.PubMed
5.
go back to reference Weiland M, Gao XH, Zhou L, Mi QS. Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol. 2012;9:850–9.CrossRef Weiland M, Gao XH, Zhou L, Mi QS. Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol. 2012;9:850–9.CrossRef
6.
go back to reference Schultz NA, Dehlendorff C, Jensen BV, Bjerregaard JK, Nielsen KR, Bojesen SE, Calatayud D, Nielsen SE, Yilmaz M, Hollander NH, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311:392–404.CrossRef Schultz NA, Dehlendorff C, Jensen BV, Bjerregaard JK, Nielsen KR, Bojesen SE, Calatayud D, Nielsen SE, Yilmaz M, Hollander NH, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311:392–404.CrossRef
7.
go back to reference Swellam M, Zahran RFK, Abo El-Sadat Taha H, El-Khazragy N, Abdel-Malak C. Role of some circulating MiRNAs on breast cancer diagnosis. Arch Physiol Biochem. 2018. [Epub ahead of print]. Swellam M, Zahran RFK, Abo El-Sadat Taha H, El-Khazragy N, Abdel-Malak C. Role of some circulating MiRNAs on breast cancer diagnosis. Arch Physiol Biochem. 2018. [Epub ahead of print].
8.
go back to reference Guo H, Qi RQ, Lv YN, Wang HX, Hong YX, Zheng S, Li JH, Gao XH, Chen HD. miR-31 is distinctively overexpressed in primary male extramammary Paget's disease. Oncotarget. 2016;7:24559–63.PubMedPubMedCentral Guo H, Qi RQ, Lv YN, Wang HX, Hong YX, Zheng S, Li JH, Gao XH, Chen HD. miR-31 is distinctively overexpressed in primary male extramammary Paget's disease. Oncotarget. 2016;7:24559–63.PubMedPubMedCentral
9.
go back to reference Zhou S, Zhong W, Mai R, Zhang G. Mammary and Extramammary Paget's disease presented different expression pattern of steroid hormone receptors. Biomed Res Int. 2017;2017:3768247.PubMedPubMedCentral Zhou S, Zhong W, Mai R, Zhang G. Mammary and Extramammary Paget's disease presented different expression pattern of steroid hormone receptors. Biomed Res Int. 2017;2017:3768247.PubMedPubMedCentral
10.
go back to reference Carbotta G, Sallustio P, Prestera A, Laforgia R, Lobascio P, Palasciano N. Perineal Paget's disease: a rare disorder and review of literature. Ann Med Surg (Lond). 2016;9:50–2.CrossRef Carbotta G, Sallustio P, Prestera A, Laforgia R, Lobascio P, Palasciano N. Perineal Paget's disease: a rare disorder and review of literature. Ann Med Surg (Lond). 2016;9:50–2.CrossRef
11.
go back to reference Murata Y, Kumano K. Extramammary Paget's disease of the genitalia with clinically clear margins can be adequately resected with 1 cm margin. Eur J Dermatol. 2005;15:168–70.PubMed Murata Y, Kumano K. Extramammary Paget's disease of the genitalia with clinically clear margins can be adequately resected with 1 cm margin. Eur J Dermatol. 2005;15:168–70.PubMed
12.
go back to reference Mohs FE, Blanchard L. Microscopically controlled surgery for extramammary Paget's disease. Arch Dermatol. 1979;115:706–8.CrossRef Mohs FE, Blanchard L. Microscopically controlled surgery for extramammary Paget's disease. Arch Dermatol. 1979;115:706–8.CrossRef
13.
go back to reference O'Connor WJ, Lim KK, Zalla MJ, Gagnot M, Otley CC, Nguyen TH, Roenigk RK. Comparison of mohs micrographic surgery and wide excision for extramammary Paget's disease. Dermatol Surg. 2003;29:723–7.CrossRef O'Connor WJ, Lim KK, Zalla MJ, Gagnot M, Otley CC, Nguyen TH, Roenigk RK. Comparison of mohs micrographic surgery and wide excision for extramammary Paget's disease. Dermatol Surg. 2003;29:723–7.CrossRef
14.
go back to reference Kang Z, Xu F, Zhu Y, Fu P, Zhang QA, Hu T, Li X, Zhang Q, Wu Z, Zhang X, et al. Genetic analysis of mismatch repair genes alterations in Extramammary Paget disease. Am J Surg Pathol. 2016;40:1517–25.CrossRef Kang Z, Xu F, Zhu Y, Fu P, Zhang QA, Hu T, Li X, Zhang Q, Wu Z, Zhang X, et al. Genetic analysis of mismatch repair genes alterations in Extramammary Paget disease. Am J Surg Pathol. 2016;40:1517–25.CrossRef
15.
go back to reference Kato J, Sumikawa Y, Hida T, Kamiya T, Horimoto K, Kamiya S, Sato S, Takahashi H, Sawada M, Yamashita T. Serum cytokeratin 19 fragment 21-1 is a useful tumor marker for the assessment of extramammary Paget's disease. J Dermatol. 2017;44:666–70.CrossRef Kato J, Sumikawa Y, Hida T, Kamiya T, Horimoto K, Kamiya S, Sato S, Takahashi H, Sawada M, Yamashita T. Serum cytokeratin 19 fragment 21-1 is a useful tumor marker for the assessment of extramammary Paget's disease. J Dermatol. 2017;44:666–70.CrossRef
16.
go back to reference Oji M, Furue M, Tamaki K. Serum carcinoembryonic antigen level in Paget's disease. Br J Dermatol. 1984;110:211–3.CrossRef Oji M, Furue M, Tamaki K. Serum carcinoembryonic antigen level in Paget's disease. Br J Dermatol. 1984;110:211–3.CrossRef
17.
go back to reference Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol. 2016;231:25–30.CrossRef Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol. 2016;231:25–30.CrossRef
18.
go back to reference Lv Y, Qi R, Xu J, Di Z, Zheng H, Huo W, Zhang L, Chen H, Gao X. Profiling of serum and urinary microRNAs in children with atopic dermatitis. PLoS One. 2014;9:e115448.CrossRef Lv Y, Qi R, Xu J, Di Z, Zheng H, Huo W, Zhang L, Chen H, Gao X. Profiling of serum and urinary microRNAs in children with atopic dermatitis. PLoS One. 2014;9:e115448.CrossRef
19.
go back to reference Kanitakis J. Mammary and extramammary Paget's disease. J Eur Acad Dermatol Venereol. 2007;21:581–90.CrossRef Kanitakis J. Mammary and extramammary Paget's disease. J Eur Acad Dermatol Venereol. 2007;21:581–90.CrossRef
20.
go back to reference Chanda JJ. Extramammary Paget's disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985;13:1009–14.CrossRef Chanda JJ. Extramammary Paget's disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985;13:1009–14.CrossRef
21.
go back to reference Merot Y, Mazoujian G, Pinkus G, Momtaz TK, Murphy GF. Extramammary Paget's disease of the perianal and perineal regions. Evidence of apocrine derivation. Arch Dermatol. 1985;121:750–2.CrossRef Merot Y, Mazoujian G, Pinkus G, Momtaz TK, Murphy GF. Extramammary Paget's disease of the perianal and perineal regions. Evidence of apocrine derivation. Arch Dermatol. 1985;121:750–2.CrossRef
22.
go back to reference Fujimoto A, Takata M, Hatta N, Takehara K. Expression of structurally unaltered androgen receptor in extramammary Paget's disease. Lab Investig. 2000;80:1465–71.CrossRef Fujimoto A, Takata M, Hatta N, Takehara K. Expression of structurally unaltered androgen receptor in extramammary Paget's disease. Lab Investig. 2000;80:1465–71.CrossRef
23.
go back to reference Mazoujian G, Pinkus GS, Haagensen DE Jr. Extramammary Paget's disease--evidence for an apocrine origin. An immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins. Am J Surg Pathol. 1984;8:43–50.CrossRef Mazoujian G, Pinkus GS, Haagensen DE Jr. Extramammary Paget's disease--evidence for an apocrine origin. An immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins. Am J Surg Pathol. 1984;8:43–50.CrossRef
24.
go back to reference Hanna W, Alowami S, Malik A. The role of HER-2/neu oncogene and vimentin filaments in the production of the Paget's phenotype. Breast J. 2003;9:485–90.CrossRef Hanna W, Alowami S, Malik A. The role of HER-2/neu oncogene and vimentin filaments in the production of the Paget's phenotype. Breast J. 2003;9:485–90.CrossRef
25.
go back to reference Giger O, Caduff R, O'Meara A, Diener PA, Knuth A, Jager D, Moch H, Varga Z. Frequent expression of the breast differentiation antigen NY-BR-1 in mammary and extramammary Paget's disease. Pathol Int. 2010;60:726–34.CrossRef Giger O, Caduff R, O'Meara A, Diener PA, Knuth A, Jager D, Moch H, Varga Z. Frequent expression of the breast differentiation antigen NY-BR-1 in mammary and extramammary Paget's disease. Pathol Int. 2010;60:726–34.CrossRef
26.
go back to reference Imam A, Yoshida SO, Taylor CR. Distinguishing tumour cells of mammary from extramammary Paget's disease using antibodies to two different glycoproteins from human milk-fat-globule membrane. Br J Cancer. 1988;58:373–8.CrossRef Imam A, Yoshida SO, Taylor CR. Distinguishing tumour cells of mammary from extramammary Paget's disease using antibodies to two different glycoproteins from human milk-fat-globule membrane. Br J Cancer. 1988;58:373–8.CrossRef
27.
go back to reference Tamaki K, Hino H, Ohara K, Furue M. Lectin-binding sites in Paget's disease. Br J Dermatol. 1985;113:17–24.CrossRef Tamaki K, Hino H, Ohara K, Furue M. Lectin-binding sites in Paget's disease. Br J Dermatol. 1985;113:17–24.CrossRef
28.
go back to reference Schwarz LJ, Hutchinson KE, Rexer BN, Estrada MV, Gonzalez Ericsson PI, Sanders ME, Dugger TC, Formisano L, Guerrero-Zotano A, Red-Brewer M, et al. An ERBB1-3 neutralizing antibody mixture with high activity against drug-resistant HER2+ breast cancers with ERBB ligand overexpression. J Natl Cancer Inst. 2017;109:1–10. Schwarz LJ, Hutchinson KE, Rexer BN, Estrada MV, Gonzalez Ericsson PI, Sanders ME, Dugger TC, Formisano L, Guerrero-Zotano A, Red-Brewer M, et al. An ERBB1-3 neutralizing antibody mixture with high activity against drug-resistant HER2+ breast cancers with ERBB ligand overexpression. J Natl Cancer Inst. 2017;109:1–10.
29.
go back to reference Choi HJ, Joo HS, Won HY, Min KW, Kim HY, Son T, Oh YH, Lee JY, Kong G. Role of RBP2-induced ER and IGF1R-ErbB signaling in tamoxifen resistance in breast Cancer. J Natl Cancer Inst. 2018;110:1–11.CrossRef Choi HJ, Joo HS, Won HY, Min KW, Kim HY, Son T, Oh YH, Lee JY, Kong G. Role of RBP2-induced ER and IGF1R-ErbB signaling in tamoxifen resistance in breast Cancer. J Natl Cancer Inst. 2018;110:1–11.CrossRef
30.
go back to reference Hou Y, Shen R, Chaudhary S, Tonkovich D, Li Z. Utility of different immunostains for diagnosis of metastatic breast carcinomas in both surgical and cytological specimens. Ann Diagn Pathol. 2017;30:21–7.CrossRef Hou Y, Shen R, Chaudhary S, Tonkovich D, Li Z. Utility of different immunostains for diagnosis of metastatic breast carcinomas in both surgical and cytological specimens. Ann Diagn Pathol. 2017;30:21–7.CrossRef
31.
go back to reference Wu H, Wang H, Guan S, Zhang J, Chen Q, Wang X, Ma K, Zhao P, Zhao H, Yao W, et al. Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status. Oncotarget. 2017;8:84996–5013.PubMedPubMedCentral Wu H, Wang H, Guan S, Zhang J, Chen Q, Wang X, Ma K, Zhao P, Zhao H, Yao W, et al. Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status. Oncotarget. 2017;8:84996–5013.PubMedPubMedCentral
32.
go back to reference Kang Z, Zhang Q, Zhang Q, Li X, Hu T, Xu X, Wu Z, Zhang X, Wang H, Xu J, et al. Clinical and pathological characteristics of extramammary Paget's disease: report of 246 Chinese male patients. Int J Clin Exp Pathol. 2015;8:13233–40.PubMedPubMedCentral Kang Z, Zhang Q, Zhang Q, Li X, Hu T, Xu X, Wu Z, Zhang X, Wang H, Xu J, et al. Clinical and pathological characteristics of extramammary Paget's disease: report of 246 Chinese male patients. Int J Clin Exp Pathol. 2015;8:13233–40.PubMedPubMedCentral
33.
go back to reference Tian W, Osawa M, Horiuchi H, Tomita Y. Expression of the prolactin-inducible protein (PIP/GCDFP15) gene in benign epithelium and adenocarcinoma of the prostate. Cancer Sci. 2004;95:491–5.CrossRef Tian W, Osawa M, Horiuchi H, Tomita Y. Expression of the prolactin-inducible protein (PIP/GCDFP15) gene in benign epithelium and adenocarcinoma of the prostate. Cancer Sci. 2004;95:491–5.CrossRef
34.
go back to reference Seipel AH, Samaratunga H, Delahunt B, Wiklund P, Clements M, Egevad L. Immunohistochemistry of ductal adenocarcinoma of the prostate and adenocarcinomas of non-prostatic origin: a comparative study. APMIS. 2016;124:263–70.CrossRef Seipel AH, Samaratunga H, Delahunt B, Wiklund P, Clements M, Egevad L. Immunohistochemistry of ductal adenocarcinoma of the prostate and adenocarcinomas of non-prostatic origin: a comparative study. APMIS. 2016;124:263–70.CrossRef
35.
go back to reference Day KC, Lorenzatti Hiles G, Kozminsky M, Dawsey SJ, Paul A, Broses LJ, Shah R, Kunja LP, Hall C, Palanisamy N, et al. HER2 and EGFR overexpression support metastatic progression of prostate Cancer to bone. Cancer Res. 2017;77:74–85.CrossRef Day KC, Lorenzatti Hiles G, Kozminsky M, Dawsey SJ, Paul A, Broses LJ, Shah R, Kunja LP, Hall C, Palanisamy N, et al. HER2 and EGFR overexpression support metastatic progression of prostate Cancer to bone. Cancer Res. 2017;77:74–85.CrossRef
36.
go back to reference Peng Y, Wang L, Gu J. Elevated preoperative carcinoembryonic antigen (CEA) and Ki67 is predictor of decreased survival in IIA stage colon cancer. World J Surg. 2013;37:208–13.CrossRef Peng Y, Wang L, Gu J. Elevated preoperative carcinoembryonic antigen (CEA) and Ki67 is predictor of decreased survival in IIA stage colon cancer. World J Surg. 2013;37:208–13.CrossRef
37.
go back to reference Ochs AM, Wong L, Kakani V, Neerukonda S, Gorske J, Rao A, Riggs M, Ward H, Keville L. Expression of vascular endothelial growth factor and HER2/neu in stage II colon cancer and correlation with survival. Clin Colorectal Cancer. 2004;4:262–7.CrossRef Ochs AM, Wong L, Kakani V, Neerukonda S, Gorske J, Rao A, Riggs M, Ward H, Keville L. Expression of vascular endothelial growth factor and HER2/neu in stage II colon cancer and correlation with survival. Clin Colorectal Cancer. 2004;4:262–7.CrossRef
38.
go back to reference Basova P, Pesta M, Sochor M, Stopka T. Prediction potential of serum miR-155 and miR-24 for relapsing early breast Cancer. Int J Mol Sci. 2017;18:E2116. Basova P, Pesta M, Sochor M, Stopka T. Prediction potential of serum miR-155 and miR-24 for relapsing early breast Cancer. Int J Mol Sci. 2017;18:E2116.
39.
go back to reference Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119:586–93.CrossRef Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119:586–93.CrossRef
40.
go back to reference Gasparini P, Lovat F, Fassan M, Casadei L, Cascione L, Jacob NK, Carasi S, Palmieri D, Costinean S, Shapiro CL, et al. Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation. Proc Natl Acad Sci U S A. 2014;111:4536–41.CrossRef Gasparini P, Lovat F, Fassan M, Casadei L, Cascione L, Jacob NK, Carasi S, Palmieri D, Costinean S, Shapiro CL, et al. Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation. Proc Natl Acad Sci U S A. 2014;111:4536–41.CrossRef
41.
go back to reference Cai ZK, Chen Q, Chen YB, Gu M, Zheng DC, Zhou J, Wang Z. microRNA-155 promotes the proliferation of prostate cancer cells by targeting annexin 7. Mol Med Rep. 2015;11:533–8.CrossRef Cai ZK, Chen Q, Chen YB, Gu M, Zheng DC, Zhou J, Wang Z. microRNA-155 promotes the proliferation of prostate cancer cells by targeting annexin 7. Mol Med Rep. 2015;11:533–8.CrossRef
42.
go back to reference Yang H, Liu C, Zhang YQ, Ge LT, Chen J, Jia XQ, Gu RX, Sun Y, Sun WD. Ilexgenin a induces B16-F10 melanoma cell G1/S arrest in vitro and reduces tumor growth in vivo. Int Immunopharmacol. 2015;24:423–31.CrossRef Yang H, Liu C, Zhang YQ, Ge LT, Chen J, Jia XQ, Gu RX, Sun Y, Sun WD. Ilexgenin a induces B16-F10 melanoma cell G1/S arrest in vitro and reduces tumor growth in vivo. Int Immunopharmacol. 2015;24:423–31.CrossRef
43.
go back to reference Cao H, Huang S, Liu A, Chen Z. Up-regulated expression of miR-155 in human colonic cancer. J Cancer Res Ther. 2018;14:604–7.CrossRef Cao H, Huang S, Liu A, Chen Z. Up-regulated expression of miR-155 in human colonic cancer. J Cancer Res Ther. 2018;14:604–7.CrossRef
44.
go back to reference Forzati F, De Martino M, Esposito F, Sepe R, Pellecchia S, Malapelle U, Pellino G, Arra C, Fusco A. miR-155 is positively regulated by CBX7 in mouse embryonic fibroblasts and colon carcinomas, and targets the KRAS oncogene. BMC Cancer. 2017;17:170.CrossRef Forzati F, De Martino M, Esposito F, Sepe R, Pellecchia S, Malapelle U, Pellino G, Arra C, Fusco A. miR-155 is positively regulated by CBX7 in mouse embryonic fibroblasts and colon carcinomas, and targets the KRAS oncogene. BMC Cancer. 2017;17:170.CrossRef
Metadata
Title
MiR-155, a potential serum marker of extramammary Paget’s disease
Authors
Hao Guo
Rui-Qun Qi
Jie Sheng
Chang Liu
Hang Ma
He-Xiao Wang
Jiu-Hong Li
Xing-Hua Gao
Yin-Sheng Wan
Hong-Duo Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4994-1

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