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Published in: Medical Oncology 2/2015

01-02-2015 | Original Paper

RBMS3 is a tumor suppressor gene that acts as a favorable prognostic marker in lung squamous cell carcinoma

Authors: Ya-nan Liang, Yu Liu, Qingwei Meng, Xiaobo Li, Fan Wang, Guodong Yao, Letian Wang, Songbin Fu, Dandan Tong

Published in: Medical Oncology | Issue 2/2015

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Abstract

Recent research indicates that RBMS3 may act as a tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). It has been reported that RBMS3 directly binds to the promoter region of c-Myc in ESCC and that β-catenin from both whole cell extracts and nuclear fractionation was significantly downregulated in RBMS3-transfected NPC cells compared to control cells. The aim of this study was to evaluate the clinical significance of the RBMS3 gene expression in relation to the expression of Wnt pathway components in patients with lung squamous cell carcinoma (LSCC). RBMS3, c-Myc and cytoplasmic β-catenin were detected in 39.76, 56.63 and 89.16 % of 83 LSCC samples by immunohistochemistry, respectively, in 83 primary LSCC samples. Semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting demonstrated decreased RBMS3 mRNA and expression in 33.33 % (10/30) and 36.67 % (11/30) tumor tissues, respectively. Statistical correlation analysis showed RBMS3 to be negatively correlated with c-Myc (r = −0.384, p < 0.001) and not correlated with cytoplasmic β-catenin in the LSCC samples. Multivariate Cox proportional hazards model analysis showed that the combined marker RBMS3/c-Myc was an independent prognostic indicator of overall survival (p = 0.001; HR 3.470; IC 95 %, 1.652–7.290), and c-Myc was a prognostic indicator of disease-free survival (p < 0.001; HR 3.182; IC 95 %, 1.961–8.920). RBMS3 is a novel TSG in LSCC, and its downregulation facilitates development and progression of LSCC. Therefore, it is suggested that Rbms3 as a tumor marker may play an important role in diagnosis of LSCC.
Literature
1.
go back to reference Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomark Prev. 2010;19(8):1893–907.CrossRef Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomark Prev. 2010;19(8):1893–907.CrossRef
2.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRef
3.
go back to reference Tyczynski JE, Bray F, Parkin DM. Lung cancer in Europe in 2000: epidemiology, prevention, and early detection. Lancet Oncol. 2003;4(1):45–55.PubMedCrossRef Tyczynski JE, Bray F, Parkin DM. Lung cancer in Europe in 2000: epidemiology, prevention, and early detection. Lancet Oncol. 2003;4(1):45–55.PubMedCrossRef
4.
go back to reference Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3(8):819–31.PubMedCrossRef Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3(8):819–31.PubMedCrossRef
5.
go back to reference Silvestri GA, Alberg AJ, Ravenel J. The changing epidemiology of lung cancer with a focus on screening. BMJ. 2009;339:b3053.PubMedCrossRef Silvestri GA, Alberg AJ, Ravenel J. The changing epidemiology of lung cancer with a focus on screening. BMJ. 2009;339:b3053.PubMedCrossRef
6.
go back to reference Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.PubMedCrossRef Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.PubMedCrossRef
7.
go back to reference Giaccone G. Oncogenes and antioncogenes in lung tumorigenesis. Chest. 1996;109(5 Suppl.):130S–4S.PubMedCrossRef Giaccone G. Oncogenes and antioncogenes in lung tumorigenesis. Chest. 1996;109(5 Suppl.):130S–4S.PubMedCrossRef
8.
go back to reference Testa JR, Liu Z, Feder M, Bell DW, Balsara B, Cheng JQ, et al. Advances in the analysis of chromosome alterations in human lung carcinomas. Cancer Genet Cytogenet. 1997;95(1):20–32.PubMedCrossRef Testa JR, Liu Z, Feder M, Bell DW, Balsara B, Cheng JQ, et al. Advances in the analysis of chromosome alterations in human lung carcinomas. Cancer Genet Cytogenet. 1997;95(1):20–32.PubMedCrossRef
9.
go back to reference Lu YJ, Dong XY, Shipley J, Zhang RG, Cheng SJ. Chromosome 3 imbalances are the most frequent aberration found in non-small cell lung carcinoma. Lung Cancer. 1999;23(1):61–6.PubMedCrossRef Lu YJ, Dong XY, Shipley J, Zhang RG, Cheng SJ. Chromosome 3 imbalances are the most frequent aberration found in non-small cell lung carcinoma. Lung Cancer. 1999;23(1):61–6.PubMedCrossRef
10.
go back to reference Hilbe W, Dirnhofer S, Greil R, Woll E. Biomarkers in non-small cell lung cancer prevention. Eur J Cancer Prev. 2004;13(5):425–36.PubMedCrossRef Hilbe W, Dirnhofer S, Greil R, Woll E. Biomarkers in non-small cell lung cancer prevention. Eur J Cancer Prev. 2004;13(5):425–36.PubMedCrossRef
11.
go back to reference Brauch H, Johnson B, Hovis J, Yano T, Gazdar A, Pettengill OS, et al. Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med. 1987;317(18):1109–13.PubMedCrossRef Brauch H, Johnson B, Hovis J, Yano T, Gazdar A, Pettengill OS, et al. Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med. 1987;317(18):1109–13.PubMedCrossRef
12.
go back to reference Hibi K, Takahashi T, Yamakawa K, Ueda R, Sekido Y, Ariyoshi Y, et al. Three distinct regions involved in 3p deletion in human lung cancer. Oncogene. 1992;7(3):445–9.PubMed Hibi K, Takahashi T, Yamakawa K, Ueda R, Sekido Y, Ariyoshi Y, et al. Three distinct regions involved in 3p deletion in human lung cancer. Oncogene. 1992;7(3):445–9.PubMed
13.
go back to reference Niki T, Izumi S, Saegusa Y, Taira T, Takai T, Iguchi-Ariga SM, et al. MSSP promotes ras/myc cooperative cell transforming activity by binding to c-Myc. Genes Cells. 2000;5(2):127–41.PubMedCrossRef Niki T, Izumi S, Saegusa Y, Taira T, Takai T, Iguchi-Ariga SM, et al. MSSP promotes ras/myc cooperative cell transforming activity by binding to c-Myc. Genes Cells. 2000;5(2):127–41.PubMedCrossRef
14.
go back to reference Penkov D, Ni R, Else C, Pinol-Roma S, Ramirez F, Tanaka S. Cloning of a human gene closely related to the genes coding for the c-myc single-strand binding proteins. Gene. 2000;243(1–2):27–36.PubMedCrossRef Penkov D, Ni R, Else C, Pinol-Roma S, Ramirez F, Tanaka S. Cloning of a human gene closely related to the genes coding for the c-myc single-strand binding proteins. Gene. 2000;243(1–2):27–36.PubMedCrossRef
15.
go back to reference Li Y, Chen L, Nie CJ, Zeng TT, Liu H, Mao X, et al. Downregulation of RBMS3 is associated with poor prognosis in esophageal squamous cell carcinoma. Cancer Res. 2011;71(19):6106–15.PubMedCrossRef Li Y, Chen L, Nie CJ, Zeng TT, Liu H, Mao X, et al. Downregulation of RBMS3 is associated with poor prognosis in esophageal squamous cell carcinoma. Cancer Res. 2011;71(19):6106–15.PubMedCrossRef
16.
go back to reference Chen J, Kwong DL, Zhu CL, Chen LL, Dong SS, Zhang LY, et al. RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell proliferation, angiogenesis, and inducing apoptosis. PLoS One. 2012;7(9):e44636.PubMedCentralPubMedCrossRef Chen J, Kwong DL, Zhu CL, Chen LL, Dong SS, Zhang LY, et al. RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell proliferation, angiogenesis, and inducing apoptosis. PLoS One. 2012;7(9):e44636.PubMedCentralPubMedCrossRef
17.
go back to reference Zajac-Kaye M. Myc oncogene: a key component in cell cycle regulation and its implication for lung cancer. Lung Cancer. 2001;34(Suppl. 2):S43–6.PubMedCrossRef Zajac-Kaye M. Myc oncogene: a key component in cell cycle regulation and its implication for lung cancer. Lung Cancer. 2001;34(Suppl. 2):S43–6.PubMedCrossRef
18.
go back to reference Xiao Q, Claassen G, Shi J, Adachi S, Sedivy J, Hann SR. Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis. Genes Dev. 1998;12(24):3803–8.PubMedCentralPubMedCrossRef Xiao Q, Claassen G, Shi J, Adachi S, Sedivy J, Hann SR. Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis. Genes Dev. 1998;12(24):3803–8.PubMedCentralPubMedCrossRef
19.
go back to reference Luo J, Xiao J, Tao Z, Li X. Detection of c-myc gene expression in nasopharyngeal carcinoma by nonradioactive in situ hybridization and immunohistochemistry. Chin Med J (Engl). 1997;110(3):229–32. Luo J, Xiao J, Tao Z, Li X. Detection of c-myc gene expression in nasopharyngeal carcinoma by nonradioactive in situ hybridization and immunohistochemistry. Chin Med J (Engl). 1997;110(3):229–32.
20.
go back to reference Porter MJ, Field JK, Leung SF, Lo D, Lee JC, Spandidos DA, et al. The detection of the c-myc and ras oncogenes in nasopharyngeal carcinoma by immunohistochemistry. Acta Otolaryngol. 1994;114(1):105–9.PubMedCrossRef Porter MJ, Field JK, Leung SF, Lo D, Lee JC, Spandidos DA, et al. The detection of the c-myc and ras oncogenes in nasopharyngeal carcinoma by immunohistochemistry. Acta Otolaryngol. 1994;114(1):105–9.PubMedCrossRef
21.
go back to reference Wang SF, Liu Q, Zhang SF, Liao DY, Xu H, Zhang WY, et al. Expressions of APC and c-Myc and its implication on non-small cell lung cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2010;41(5):822–6.PubMed Wang SF, Liu Q, Zhang SF, Liao DY, Xu H, Zhang WY, et al. Expressions of APC and c-Myc and its implication on non-small cell lung cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2010;41(5):822–6.PubMed
22.
go back to reference Jung J, Kim EJ, Chung HK, Park HJ, Jeong SY, Choi EK. c-Myc down-regulation is involved in proteasome inhibitor-mediated enhancement of radiotherapeutic efficacy in non-small cell lung cancer. Int J Oncol. 2012;40(2):385–90.PubMed Jung J, Kim EJ, Chung HK, Park HJ, Jeong SY, Choi EK. c-Myc down-regulation is involved in proteasome inhibitor-mediated enhancement of radiotherapeutic efficacy in non-small cell lung cancer. Int J Oncol. 2012;40(2):385–90.PubMed
23.
go back to reference Seo SK, Jin HO, Woo SH, Kim YS, An S, Lee JH, et al. Histone deacetylase inhibitors sensitize human non-small cell lung cancer cells to ionizing radiation through acetyl p53-mediated c-myc down-regulation. J Thorac Oncol. 2011;6(8):1313–9.PubMedCrossRef Seo SK, Jin HO, Woo SH, Kim YS, An S, Lee JH, et al. Histone deacetylase inhibitors sensitize human non-small cell lung cancer cells to ionizing radiation through acetyl p53-mediated c-myc down-regulation. J Thorac Oncol. 2011;6(8):1313–9.PubMedCrossRef
24.
go back to reference Komiya K, Sueoka-Aragane N, Sato A, Hisatomi T, Sakuragi T, Mitsuoka M, et al. Expression of Mina53, a novel c-Myc target gene, is a favorable prognostic marker in early stage lung cancer. Lung Cancer. 2010;69(2):232–8.PubMedCrossRef Komiya K, Sueoka-Aragane N, Sato A, Hisatomi T, Sakuragi T, Mitsuoka M, et al. Expression of Mina53, a novel c-Myc target gene, is a favorable prognostic marker in early stage lung cancer. Lung Cancer. 2010;69(2):232–8.PubMedCrossRef
25.
go back to reference Zhou W, Feng X, Ren C, Jiang X, Liu W, Huang W, et al. Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma. Mol Cancer. 2013;12:53.PubMedCentralPubMedCrossRef Zhou W, Feng X, Ren C, Jiang X, Liu W, Huang W, et al. Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma. Mol Cancer. 2013;12:53.PubMedCentralPubMedCrossRef
26.
go back to reference Chujo M, Noguchi T, Miura T, Arinaga M, Uchida Y, Tagawa Y. Comparative genomic hybridization analysis detected frequent overrepresentation of chromosome 3q in squamous cell carcinoma of the lung. Lung Cancer. 2002;38(1):23–9.PubMedCrossRef Chujo M, Noguchi T, Miura T, Arinaga M, Uchida Y, Tagawa Y. Comparative genomic hybridization analysis detected frequent overrepresentation of chromosome 3q in squamous cell carcinoma of the lung. Lung Cancer. 2002;38(1):23–9.PubMedCrossRef
27.
go back to reference Ooi AT, Gower AC, Zhang KX, Vick JL, Hong L, Nagao B, et al. Molecular profiling of premalignant lesions in lung squamous cell carcinomas identifies mechanisms involved in stepwise carcinogenesis. Cancer Prev Res (Phila). 2014;7(5):487–95.CrossRef Ooi AT, Gower AC, Zhang KX, Vick JL, Hong L, Nagao B, et al. Molecular profiling of premalignant lesions in lung squamous cell carcinomas identifies mechanisms involved in stepwise carcinogenesis. Cancer Prev Res (Phila). 2014;7(5):487–95.CrossRef
28.
go back to reference Jayasena CS, Bronner ME. Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-beta signaling. J Cell Biol. 2012;199(3):453–66.PubMedCentralPubMedCrossRef Jayasena CS, Bronner ME. Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-beta signaling. J Cell Biol. 2012;199(3):453–66.PubMedCentralPubMedCrossRef
29.
go back to reference Hu FY, Wang LP, Hou LL, Yin G, Wang HC. The expressions of STAT3, WWOX and c-myc in human non small cell lung cancer tissue and correlativity analysis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010;26(12):1203–5.PubMed Hu FY, Wang LP, Hou LL, Yin G, Wang HC. The expressions of STAT3, WWOX and c-myc in human non small cell lung cancer tissue and correlativity analysis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010;26(12):1203–5.PubMed
30.
go back to reference Seo AN, Yang JM, Kim H, Jheon S, Kim K, Lee CT, et al. Clinicopathologic and prognostic significance of c-MYC copy number gain in lung adenocarcinomas. Br J Cancer. 2014;110(11):2688–99.PubMedCrossRef Seo AN, Yang JM, Kim H, Jheon S, Kim K, Lee CT, et al. Clinicopathologic and prognostic significance of c-MYC copy number gain in lung adenocarcinomas. Br J Cancer. 2014;110(11):2688–99.PubMedCrossRef
31.
go back to reference Nakayama S, Sng N, Carretero J, Welner R, Hayashi Y, Yamamoto M, et al. beta-catenin contributes to lung tumor development induced by EGFR mutations. Cancer Res. 2014;74(20):5891–902. Nakayama S, Sng N, Carretero J, Welner R, Hayashi Y, Yamamoto M, et al. beta-catenin contributes to lung tumor development induced by EGFR mutations. Cancer Res. 2014;74(20):5891–902.
32.
go back to reference Fan K, Li N, Qi J, Yin P, Zhao C, Wang L, et al. Wnt/beta-catenin signaling induces the transcription of cystathionine-gamma-lyase, a stimgulator of tumor in colon cancer. Cell Signal. 2014;26(12):2801–8. Fan K, Li N, Qi J, Yin P, Zhao C, Wang L, et al. Wnt/beta-catenin signaling induces the transcription of cystathionine-gamma-lyase, a stimgulator of tumor in colon cancer. Cell Signal. 2014;26(12):2801–8.
Metadata
Title
RBMS3 is a tumor suppressor gene that acts as a favorable prognostic marker in lung squamous cell carcinoma
Authors
Ya-nan Liang
Yu Liu
Qingwei Meng
Xiaobo Li
Fan Wang
Guodong Yao
Letian Wang
Songbin Fu
Dandan Tong
Publication date
01-02-2015
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2015
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0459-9

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