Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2012

Open Access 01-12-2012 | Research

Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival

Authors: Chun-Hui Zhou, Li-Ping Ye, Shi-Xing Ye, Yan Li, Xin-Yin Zhang, Xin-Yu Xu, Li-Yun Gong

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

Login to get access

Abstract

Background

Sex determining region Y (SRY)-related high mobility groupbox 9 (SOX9) is an important transcription factor required for development, which regulates the expression of target genes in the associated pathway. The aim of this study was to describe the expression of SOX9 in human non-small cell lung cancer (NSCLC) and to investigate the association between SOX9 expression and progression of NSCLC.

Methods

SOX9 protein and mRNA expression in normal human pneumonocytes, lung cancer cell lines, and eight pairs of matched lung cancer tissues and their adjacent normal lung tissues were detected by Western blotting and real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was used to determine SOX9 protein expression in 142 cases of histologically characterized NSCLC. Statistical analyses were applied to test for prognostic and diagnostic associations.

Results

SOX9 in lung cancer cell lines was upregulated at both mRNA and protein levels, and SOX9 mRNA and protein were also elevated in NSCLC tissues compared with levels in corresponding adjacent non-cancerous lung tissues. Immunohistochemical analysis demonstrated a high expression of SOX9 in 74/142 (52.1%) paraffin-embedded archival lung cancer biopsies. Statistical analysis indicated that upregulation of SOX9 was significantly correlated with the histological stage of NSCLC (P = 0.017) and that patients with a high SOX9 level exhibited a shorter survival time (P < 0.001). Multivariate analysis illustrated that SOX9 upregulation might be an independent prognostic indicator for the survival of patients with NSCLC.

Conclusions

This work shows that SOX9 may serve as a novel and prognostic marker for NSCLC, and play a role during the development and progression of the disease.
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 (2): 69-90. 10.3322/caac.20107.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61 (2): 69-90. 10.3322/caac.20107.CrossRefPubMed
2.
go back to reference Lung Carcinoma: Tumors of the Lungs. Merck Manual Professional. 2008, 2011: Lung Carcinoma: Tumors of the Lungs. Merck Manual Professional. 2008, 2011:
3.
go back to reference Harley VR, Clarkson MJ, Argentaro A: The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]. Endocr Rev. 2003, 24 (4): 466-487. 10.1210/er.2002-0025.CrossRefPubMed Harley VR, Clarkson MJ, Argentaro A: The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]. Endocr Rev. 2003, 24 (4): 466-487. 10.1210/er.2002-0025.CrossRefPubMed
4.
go back to reference Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, Pasantes J, Bricarelli FD, Keutel J, Hustert E, et al: Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 1994, 79 (6): 1111-1120. 10.1016/0092-8674(94)90041-8.CrossRefPubMed Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, Pasantes J, Bricarelli FD, Keutel J, Hustert E, et al: Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 1994, 79 (6): 1111-1120. 10.1016/0092-8674(94)90041-8.CrossRefPubMed
5.
go back to reference Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanovic M, Weissenbach J, Mansour S, Young ID, Goodfellow PN, et al: Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 1994, 372 (6506): 525-530. 10.1038/372525a0.CrossRefPubMed Foster JW, Dominguez-Steglich MA, Guioli S, Kwok C, Weller PA, Stevanovic M, Weissenbach J, Mansour S, Young ID, Goodfellow PN, et al: Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 1994, 372 (6506): 525-530. 10.1038/372525a0.CrossRefPubMed
6.
go back to reference Jiang SS, Fang WT, Hou YH, Huang SF, Yen BL, Chang JL, Li SM, Liu HP, Liu YL, Huang CT, et al: Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. Clin Cancer Res. 2010, 16 (17): 4363-4373. 10.1158/1078-0432.CCR-10-0138.CrossRefPubMed Jiang SS, Fang WT, Hou YH, Huang SF, Yen BL, Chang JL, Li SM, Liu HP, Liu YL, Huang CT, et al: Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. Clin Cancer Res. 2010, 16 (17): 4363-4373. 10.1158/1078-0432.CCR-10-0138.CrossRefPubMed
7.
go back to reference Muller P, Crofts JD, Newman BS, Bridgewater LC, Lin CY, Gustafsson JA, Strom A: SOX9 mediates the retinoic acid-induced HES-1 gene expression in human breast cancer cells. Breast Cancer Res Treat. 2010, 120 (2): 317-326. 10.1007/s10549-009-0381-6.CrossRefPubMed Muller P, Crofts JD, Newman BS, Bridgewater LC, Lin CY, Gustafsson JA, Strom A: SOX9 mediates the retinoic acid-induced HES-1 gene expression in human breast cancer cells. Breast Cancer Res Treat. 2010, 120 (2): 317-326. 10.1007/s10549-009-0381-6.CrossRefPubMed
8.
go back to reference Lu B, Fang Y, Xu J, Wang L, Xu F, Xu E, Huang Q, Lai M: Analysis of SOX9 expression in colorectal cancer. Am J Clin Pathol. 2008, 130 (6): 897-904. 10.1309/AJCPW1W8GJBQGCNI.CrossRefPubMed Lu B, Fang Y, Xu J, Wang L, Xu F, Xu E, Huang Q, Lai M: Analysis of SOX9 expression in colorectal cancer. Am J Clin Pathol. 2008, 130 (6): 897-904. 10.1309/AJCPW1W8GJBQGCNI.CrossRefPubMed
9.
go back to reference Wang H, Leav I, Ibaragi S, Wegner M, Hu GF, Lu ML, Balk SP, Yuan X: SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion. Cancer Res. 2008, 68 (6): 1625-1630. 10.1158/0008-5472.CAN-07-5915.CrossRefPubMed Wang H, Leav I, Ibaragi S, Wegner M, Hu GF, Lu ML, Balk SP, Yuan X: SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion. Cancer Res. 2008, 68 (6): 1625-1630. 10.1158/0008-5472.CAN-07-5915.CrossRefPubMed
10.
go back to reference Ibrahim L, Dominguez M, Yacoub M: Primary human adult lung epithelial cells in vitro: response to interferon-gamma and cytomegalovirus. Immunology. 1993, 79 (1): 119-124.PubMedCentralPubMed Ibrahim L, Dominguez M, Yacoub M: Primary human adult lung epithelial cells in vitro: response to interferon-gamma and cytomegalovirus. Immunology. 1993, 79 (1): 119-124.PubMedCentralPubMed
11.
go back to reference American Joint Committee on Cancer. Cancer Staging Manual. 2010, Springer, 7 American Joint Committee on Cancer. Cancer Staging Manual. 2010, Springer, 7
12.
go back to reference Li J, Guan HY, Gong LY, Song LB, Zhang N, Wu J, Yuan J, Zheng YJ, Huang ZS, Li M: Clinical significance of sphingosine kinase-1 expression in human astrocytomas progression and overall patient survival. Clin Cancer Res. 2008, 14 (21): 6996-7003. 10.1158/1078-0432.CCR-08-0754.CrossRefPubMed Li J, Guan HY, Gong LY, Song LB, Zhang N, Wu J, Yuan J, Zheng YJ, Huang ZS, Li M: Clinical significance of sphingosine kinase-1 expression in human astrocytomas progression and overall patient survival. Clin Cancer Res. 2008, 14 (21): 6996-7003. 10.1158/1078-0432.CCR-08-0754.CrossRefPubMed
13.
go back to reference Li J, Gong LY, Song LB, Jiang LL, Liu LP, Wu J, Yuan J, Cai JC, He M, Wang L, et al: Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-kappaB Pathway. Am J Pathol. 2010, 176 (2): 699-709. 10.2353/ajpath.2010.090502.PubMedCentralCrossRefPubMed Li J, Gong LY, Song LB, Jiang LL, Liu LP, Wu J, Yuan J, Cai JC, He M, Wang L, et al: Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-kappaB Pathway. Am J Pathol. 2010, 176 (2): 699-709. 10.2353/ajpath.2010.090502.PubMedCentralCrossRefPubMed
14.
go back to reference Dupasquier S, Abdel-Samad R, Glazer RI, Bastide P, Jay P, Joubert D, Cavailles V, Blache P, Quittau-Prevostel C: A new mechanism of SOX9 action to regulate PKCalpha expression in the intestine epithelium. J Cell Sci. 2009, 122 (Pt 13): 2191-2196.CrossRefPubMed Dupasquier S, Abdel-Samad R, Glazer RI, Bastide P, Jay P, Joubert D, Cavailles V, Blache P, Quittau-Prevostel C: A new mechanism of SOX9 action to regulate PKCalpha expression in the intestine epithelium. J Cell Sci. 2009, 122 (Pt 13): 2191-2196.CrossRefPubMed
15.
go back to reference Darido C, Buchert M, Pannequin J, Bastide P, Zalzali H, Mantamadiotis T, Bourgaux JF, Garambois V, Jay P, Blache P, et al: Defective claudin-7 regulation by Tcf-4 and Sox-9 disrupts the polarity and increases the tumorigenicity of colorectal cancer cells. Cancer Res. 2008, 68 (11): 4258-4268. 10.1158/0008-5472.CAN-07-5805.CrossRefPubMed Darido C, Buchert M, Pannequin J, Bastide P, Zalzali H, Mantamadiotis T, Bourgaux JF, Garambois V, Jay P, Blache P, et al: Defective claudin-7 regulation by Tcf-4 and Sox-9 disrupts the polarity and increases the tumorigenicity of colorectal cancer cells. Cancer Res. 2008, 68 (11): 4258-4268. 10.1158/0008-5472.CAN-07-5805.CrossRefPubMed
16.
go back to reference Okubo T, Knoepfler PS, Eisenman RN, Hogan BL: Nmyc plays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation. Development. 2005, 132 (6): 1363-1374. 10.1242/dev.01678.CrossRefPubMed Okubo T, Knoepfler PS, Eisenman RN, Hogan BL: Nmyc plays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation. Development. 2005, 132 (6): 1363-1374. 10.1242/dev.01678.CrossRefPubMed
17.
go back to reference Thomsen MK, Ambroisine L, Wynn S, Cheah KS, Foster CS, Fisher G, Berney DM, Moller H, Reuter VE, Scardino P, et al: SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation. Cancer Res. 2010, 70 (3): 979-987. 10.1158/0008-5472.CAN-09-2370.PubMedCentralCrossRefPubMed Thomsen MK, Ambroisine L, Wynn S, Cheah KS, Foster CS, Fisher G, Berney DM, Moller H, Reuter VE, Scardino P, et al: SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation. Cancer Res. 2010, 70 (3): 979-987. 10.1158/0008-5472.CAN-09-2370.PubMedCentralCrossRefPubMed
18.
go back to reference Carbonnelle-Puscian A, Vidal V, Laurendeau I, Valeyrie-Allanore L, Vidaud D, Bieche I, Leroy K, Lantieri L, Wolkenstein P, Schedl A, et al: SOX9 expression increases with malignant potential in tumors from patients with neurofibromatosis 1 and is not correlated to desert hedgehog. Hum Pathol. 2011, 42 (3): 434-443. 10.1016/j.humpath.2010.02.020.CrossRefPubMed Carbonnelle-Puscian A, Vidal V, Laurendeau I, Valeyrie-Allanore L, Vidaud D, Bieche I, Leroy K, Lantieri L, Wolkenstein P, Schedl A, et al: SOX9 expression increases with malignant potential in tumors from patients with neurofibromatosis 1 and is not correlated to desert hedgehog. Hum Pathol. 2011, 42 (3): 434-443. 10.1016/j.humpath.2010.02.020.CrossRefPubMed
19.
go back to reference Ling S, Chang X, Schultz L, Lee TK, Chaux A, Marchionni L, Netto GJ, Sidransky D, Berman DM: An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res. 2011, 71 (11): 3812-3821. 10.1158/0008-5472.CAN-10-3072.PubMedCentralCrossRefPubMed Ling S, Chang X, Schultz L, Lee TK, Chaux A, Marchionni L, Netto GJ, Sidransky D, Berman DM: An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res. 2011, 71 (11): 3812-3821. 10.1158/0008-5472.CAN-10-3072.PubMedCentralCrossRefPubMed
Metadata
Title
Clinical significance of SOX9 in human non-small cell lung cancer progression and overall patient survival
Authors
Chun-Hui Zhou
Li-Ping Ye
Shi-Xing Ye
Yan Li
Xin-Yin Zhang
Xin-Yu Xu
Li-Yun Gong
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-31-18

Other articles of this Issue 1/2012

Journal of Experimental & Clinical Cancer Research 1/2012 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