Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2013

Open Access 01-12-2013 | Research

Expression of seven stem-cell-associated markers in human airway biopsy specimens obtained via fiberoptic bronchoscopy

Authors: Laodong Li, Huina Yu, Xiaoyang Wang, Jinrong Zeng, Dangyu Li, Jingyan Lu, Changming Wang, Jiying Wang, Jianghong Wei, Ming Jiang, Biwen Mo

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2013

Login to get access

Abstract

Background

Previous reports have suggested that malignant transformations originate from adult stem cells, and may thus express the stem-cell-associated markers. The purpose of this study is to investigate the differential expression and clinical significance of seven stem-cell-associated markers (Bmi1, CD133, CD44, Sox2, Nanog, OCT4 and Msi2) in lung cancer, providing new targets for the diagnosis and treatment of lung cancer.

Methods

In this study, we evaluated the differential expression of mRNA levels seven stem-cell-associated markers by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) from 112 human lung cancer and 18 non-cancer tissues obtained by bronchoscopy. We further verified the differential expression of these markers by immunohistochemistry in 50 lung cancer specimens, 30 benign inflammatory lesion tissues and 20 non-tumor adjacent lung tissues.

Results

With the exception of OCT4, other markers Bmi1, CD133, CD44, Sox2, Nanog and Msi2 mRNA and protein were abundantly expressed in lung cancer. Additionally, Nanog expression was highly upregulated in lung cancer tissues and rarely presented in non-cancerous lung tissues, the sensitivity and specificity of Nanog mRNA reached 63.4% and 66.7%, respectively. Nanog therefore possessed high diagnostic value, however, CD44, Bmi1 and CD133 showed poor diagnostic value in lung cancer.

Conclusion

Nanog may serve as a promising diagnostic marker of lung cancer and potential therapeutic target in lung cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRef
2.
go back to reference Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012, 62: 10-29. 10.3322/caac.20138.CrossRef Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012, 62: 10-29. 10.3322/caac.20138.CrossRef
3.
go back to reference Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414: 105-111. 10.1038/35102167.CrossRef Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414: 105-111. 10.1038/35102167.CrossRef
4.
go back to reference Visvader JE, Lindeman GJ: Cancer stem cells in solid tumours:accumulating evidence and unresolved questions. Nat Rev Cancer. 2008, 8: 755-768. 10.1038/nrc2499.CrossRef Visvader JE, Lindeman GJ: Cancer stem cells in solid tumours:accumulating evidence and unresolved questions. Nat Rev Cancer. 2008, 8: 755-768. 10.1038/nrc2499.CrossRef
5.
go back to reference Hassan KA, Chen G, Kalemkerian GP, Wicha MS, Beer DG: An embryonic stem cell-like signature identifies poorly differentiated lung adenocarcinoma but not squamous cell carcinoma. Clin Cancer Res. 2009, 15: 6386-6390. 10.1158/1078-0432.CCR-09-1105.CrossRef Hassan KA, Chen G, Kalemkerian GP, Wicha MS, Beer DG: An embryonic stem cell-like signature identifies poorly differentiated lung adenocarcinoma but not squamous cell carcinoma. Clin Cancer Res. 2009, 15: 6386-6390. 10.1158/1078-0432.CCR-09-1105.CrossRef
6.
go back to reference Nguyen GH, Murph MM, Chang JY: Cancer stem cell radioresistance and enrichment: where frontline radiation therapy May fail in lung and esophageal cancers. Cancers. 2011, 3: 1232-1252. 10.3390/cancers3011232.CrossRef Nguyen GH, Murph MM, Chang JY: Cancer stem cell radioresistance and enrichment: where frontline radiation therapy May fail in lung and esophageal cancers. Cancers. 2011, 3: 1232-1252. 10.3390/cancers3011232.CrossRef
7.
go back to reference Pine SR, Marshall B, Varticovski L: Lung cancer stem cells. Dis Markers. 2008, 24: 257-266. 10.1155/2008/396281.CrossRef Pine SR, Marshall B, Varticovski L: Lung cancer stem cells. Dis Markers. 2008, 24: 257-266. 10.1155/2008/396281.CrossRef
8.
go back to reference Saeki M, Kobayashi D, Tsuji N, Kuribayashi K, Watanabe N: Diagnostic importance of overexpression of Bmi-1 mRNA in early breast cancers. Int J Oncol. 2009, 35: 511-515. Saeki M, Kobayashi D, Tsuji N, Kuribayashi K, Watanabe N: Diagnostic importance of overexpression of Bmi-1 mRNA in early breast cancers. Int J Oncol. 2009, 35: 511-515.
9.
go back to reference Chen YC, Hsu HS, Chen YW, Tsai TH, How CK, Wang CY, et al: Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One. 2008, 3: e2637-10.1371/journal.pone.0002637.CrossRef Chen YC, Hsu HS, Chen YW, Tsai TH, How CK, Wang CY, et al: Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One. 2008, 3: e2637-10.1371/journal.pone.0002637.CrossRef
10.
go back to reference Moreira AL, Gonen M, Rekhtman N, Downey RJ: Progenitor stem cell marker expression by pulmonary carcinomas. Mod Pathol. 2010, 23: 889-895. 10.1038/modpathol.2010.68.CrossRef Moreira AL, Gonen M, Rekhtman N, Downey RJ: Progenitor stem cell marker expression by pulmonary carcinomas. Mod Pathol. 2010, 23: 889-895. 10.1038/modpathol.2010.68.CrossRef
11.
go back to reference Leung EL, Fiscus RR, Tung JW, Tin VP, Cheng LC, Sihoe AD, et al: Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One. 2010, 5: e14062-10.1371/journal.pone.0014062.CrossRef Leung EL, Fiscus RR, Tung JW, Tin VP, Cheng LC, Sihoe AD, et al: Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One. 2010, 5: e14062-10.1371/journal.pone.0014062.CrossRef
12.
go back to reference Miyake H, Hara I, Gohji K, Yamanaka K, Arakawa S, Kamidono S: Urinary cytology and competitive reverse transcriptase-polymerase chain reaction analysis of a specific CD44 variant to detect and monitor bladder cancer. J Urol. 1998, 160: 2004-2008. 10.1016/S0022-5347(01)62225-0.CrossRef Miyake H, Hara I, Gohji K, Yamanaka K, Arakawa S, Kamidono S: Urinary cytology and competitive reverse transcriptase-polymerase chain reaction analysis of a specific CD44 variant to detect and monitor bladder cancer. J Urol. 1998, 160: 2004-2008. 10.1016/S0022-5347(01)62225-0.CrossRef
13.
go back to reference Müller FJ, Laurent LC, Kostka D, Ulitsky I, Williams R, Lu C, et al: Regulatory networks define phenotypic classes of human stem cell lines. Nature. 2008, 455: 401-405. 10.1038/nature07213.CrossRef Müller FJ, Laurent LC, Kostka D, Ulitsky I, Williams R, Lu C, et al: Regulatory networks define phenotypic classes of human stem cell lines. Nature. 2008, 455: 401-405. 10.1038/nature07213.CrossRef
14.
go back to reference Chapman CJ, Thorpe AJ, Murray A, Parsy-Kowalska CB, Allen J, Stafford KM, et al: Immunobiomarkers in small cell lung cancer: potential early cancer signals. Clin Cancer Res. 2011, 17: 1474-1480. 10.1158/1078-0432.CCR-10-1363.CrossRef Chapman CJ, Thorpe AJ, Murray A, Parsy-Kowalska CB, Allen J, Stafford KM, et al: Immunobiomarkers in small cell lung cancer: potential early cancer signals. Clin Cancer Res. 2011, 17: 1474-1480. 10.1158/1078-0432.CCR-10-1363.CrossRef
15.
go back to reference Karoubi G, Cortes-Dericks L, Gugger M, Galetta D, Spaggiari L, Schmid RA: Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma. J Surg Oncol. 2010, 102: 689-698. 10.1002/jso.21665.CrossRef Karoubi G, Cortes-Dericks L, Gugger M, Galetta D, Spaggiari L, Schmid RA: Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma. J Surg Oncol. 2010, 102: 689-698. 10.1002/jso.21665.CrossRef
16.
go back to reference Nirasawa S, Kobayashi D, Tsuji N, Kuribayashi K, Watanabe N: Diagnostic relevance of overexpressed nanog gene in early lung cancers. Oncol Rep. 2009, 22: 587-591. Nirasawa S, Kobayashi D, Tsuji N, Kuribayashi K, Watanabe N: Diagnostic relevance of overexpressed nanog gene in early lung cancers. Oncol Rep. 2009, 22: 587-591.
17.
go back to reference Sakakibara S, Nakamura Y, Satoh H, Okano H: Rna-binding protein Musashi2: developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS. J Neurosci. 2001, 21: 8091-8107. Sakakibara S, Nakamura Y, Satoh H, Okano H: Rna-binding protein Musashi2: developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS. J Neurosci. 2001, 21: 8091-8107.
18.
go back to reference Kharas MG, Lengner CJ, Al-Shahrour F, Bullinger L, Ball B, Zaidi S, et al: Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nat Med. 2010, 16: 903-908. 10.1038/nm.2187.CrossRef Kharas MG, Lengner CJ, Al-Shahrour F, Bullinger L, Ball B, Zaidi S, et al: Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nat Med. 2010, 16: 903-908. 10.1038/nm.2187.CrossRef
19.
go back to reference El-Bayoumi E, Silvestri GA: Bronchoscopy for the diagnosis and staging of lung cancer. Semin Respir Crit Care Med. 2008, 29: 261-270. 10.1055/s-2008-1076746.CrossRef El-Bayoumi E, Silvestri GA: Bronchoscopy for the diagnosis and staging of lung cancer. Semin Respir Crit Care Med. 2008, 29: 261-270. 10.1055/s-2008-1076746.CrossRef
20.
go back to reference Ezeh UI, Turek PJ, Reijo RA, Clark AT: Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer. 2005, 104: 2255-2265. 10.1002/cncr.21432.CrossRef Ezeh UI, Turek PJ, Reijo RA, Clark AT: Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer. 2005, 104: 2255-2265. 10.1002/cncr.21432.CrossRef
21.
go back to reference Lin T, Ding YQ, Li JM: Overexpression of nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol. 2012, 29: 878-885. 10.1007/s12032-011-9860-9.CrossRef Lin T, Ding YQ, Li JM: Overexpression of nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol. 2012, 29: 878-885. 10.1007/s12032-011-9860-9.CrossRef
22.
go back to reference Meng HM, Zheng P, Wang XY, Liu C, Sui HM, Wu SJ, et al: Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther. 2010, 9: 295-302. 10.4161/cbt.9.4.10666.CrossRef Meng HM, Zheng P, Wang XY, Liu C, Sui HM, Wu SJ, et al: Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther. 2010, 9: 295-302. 10.4161/cbt.9.4.10666.CrossRef
23.
go back to reference Niu CS, Li DX, Liu YH, Fu XM, Tang SF, Li J: Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells. Oncol Rep. 2011, 26: 593-601. Niu CS, Li DX, Liu YH, Fu XM, Tang SF, Li J: Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells. Oncol Rep. 2011, 26: 593-601.
24.
go back to reference Pan Y, Jiao J, Zhou C, Cheng Q, Hu Y, Chen H: Nanog is highly expressed in ovarian serous cystadenocarcinoma and correlated with clinical stage and pathological grade. Pathobiology. 2010, 77: 283-288. 10.1159/000320866.CrossRef Pan Y, Jiao J, Zhou C, Cheng Q, Hu Y, Chen H: Nanog is highly expressed in ovarian serous cystadenocarcinoma and correlated with clinical stage and pathological grade. Pathobiology. 2010, 77: 283-288. 10.1159/000320866.CrossRef
25.
go back to reference Kikuchi J, Kinoshita I, Shimizu Y, Kikuchi E, Konishi J, Oizumi S, et al: Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance. Cancer. 2010, 116: 3015-3024. 10.1002/cncr.25128.CrossRef Kikuchi J, Kinoshita I, Shimizu Y, Kikuchi E, Konishi J, Oizumi S, et al: Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance. Cancer. 2010, 116: 3015-3024. 10.1002/cncr.25128.CrossRef
26.
go back to reference Woo T, Okudela K, Mitsui H, Yazawa T, Ogawa N, Tajiri M, et al: Prognostic value of CD133 expression in stage I lung adenocarcinomas. Int J Clin Exp Pathol. 2010, 4: 32-42. Woo T, Okudela K, Mitsui H, Yazawa T, Ogawa N, Tajiri M, et al: Prognostic value of CD133 expression in stage I lung adenocarcinomas. Int J Clin Exp Pathol. 2010, 4: 32-42.
27.
go back to reference Sholl LM, Long KB, Hornick JL: Sox2 Expression in pulmonary non-small cell and neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol. 2010, 18: 55-61. 10.1097/PAI.0b013e3181b16b88.CrossRef Sholl LM, Long KB, Hornick JL: Sox2 Expression in pulmonary non-small cell and neuroendocrine carcinomas. Appl Immunohistochem Mol Morphol. 2010, 18: 55-61. 10.1097/PAI.0b013e3181b16b88.CrossRef
28.
go back to reference Lu Y, Futtner C, Rock JR, Xu X, Whitworth W, Hogan BL, et al: Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One. 2010, 5: e11022-10.1371/journal.pone.0011022.CrossRef Lu Y, Futtner C, Rock JR, Xu X, Whitworth W, Hogan BL, et al: Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One. 2010, 5: e11022-10.1371/journal.pone.0011022.CrossRef
29.
go back to reference Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, et al: Coexpression of oct4 and nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010, 70: 10433-10444. 10.1158/0008-5472.CAN-10-2638.CrossRef Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, et al: Coexpression of oct4 and nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010, 70: 10433-10444. 10.1158/0008-5472.CAN-10-2638.CrossRef
30.
go back to reference Cantz T, Key G, Bleidissel M, Gentile L, Han DW, Brenne A, et al: Absence of OCT4 expression in somatic tumor cell lines. Stem Cells. 2008, 26: 692-697. 10.1634/stemcells.2007-0657.CrossRef Cantz T, Key G, Bleidissel M, Gentile L, Han DW, Brenne A, et al: Absence of OCT4 expression in somatic tumor cell lines. Stem Cells. 2008, 26: 692-697. 10.1634/stemcells.2007-0657.CrossRef
31.
go back to reference Vrzalikova K, Skarda J, Ehrmann J, Murray PG, Fridman E, Kopolovic J, et al: Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study. J Cancer Res Clin Oncol. 2008, 134: 1037-1042. 10.1007/s00432-008-0361-y.CrossRef Vrzalikova K, Skarda J, Ehrmann J, Murray PG, Fridman E, Kopolovic J, et al: Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study. J Cancer Res Clin Oncol. 2008, 134: 1037-1042. 10.1007/s00432-008-0361-y.CrossRef
Metadata
Title
Expression of seven stem-cell-associated markers in human airway biopsy specimens obtained via fiberoptic bronchoscopy
Authors
Laodong Li
Huina Yu
Xiaoyang Wang
Jinrong Zeng
Dangyu Li
Jingyan Lu
Changming Wang
Jiying Wang
Jianghong Wei
Ming Jiang
Biwen Mo
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2013
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-32-28

Other articles of this Issue 1/2013

Journal of Experimental & Clinical Cancer Research 1/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine