Osteopontin Genetic Variants Are Associated with Overall Survival in Advanced Non-small-cell Lung Cancer Patients and Bone Metastasis

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2013 Jul 26

PMID 23883434

Citations 28

Authors

Yunzhen Chen

HaiChun Liu

Wenliang Wu

Yi Li

Jianmin Li

Affiliations

Soon will be listed here.

Abstract

Purpose: Osteopontin (OPN) plays important roles in the modulation of apoptosis, angiogenesis, immune response, and tumor invasion. Elevated osteopontin expression has been reported in the lung cancer tissues compared to counterpart normal tissues. This study examined whether genetic variations in the osteopontin gene are associated with survival of lung cancer patients and occurrence rate of bone metastasis.

Experimental Design: Three hundred and sixty patients with stages I to IV between 2003 and 2007 were recruited in this study and same number of healthy persons were used as control. Three promoter osteopontin polymorphisms, OPN-66 T/G, -156G/GG, and -443C/T variants were genotyped using DNA from blood lymphocytes. Chi-square test and a Fisher's exact test were used to analyze the genotype distribution among TNM stages and incidence of bone metastasis and lymph mode metastasis. Kaplan-Meier method and log-rank test were used to compare survival by different genotypes.

Results: For the variant at nt -443 (CC), there was a significant difference between the number of patients with stage IV and those with all other stages of lung cancer (p < 0.01). Patients with -443 (CC) variant had significant higher incidence of bone metastasis development compared to other genotypes. For the variant at nt -443 (CT), there was a significant difference between the number of lung cancer patients with stage III + IV and those with stage I + II (P < 0.01). The survival rates for patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T).

Conclusion: OSTEOPONTIN -443C/T polymorphism is a potential predictive marker of survival in lung cancer patients, it is correlated with bone metastasis significantly.

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References

Brown L, Berse B, Manseau E, Tognazzi K, Perruzzi C, Dvorak H . Osteopontin expression and distribution in human carcinomas. Am J Pathol. 1994; 145(3):610-23. PMC: 1890312. View

Liu S, Olive P, Bristow R . Biomarkers for DNA DSB inhibitors and radiotherapy clinical trials. Cancer Metastasis Rev. 2008; 27(3):445-58. DOI: 10.1007/s10555-008-9137-8. View

Santini D, Schiavon G, Vincenzi B, Gaeta L, Pantano F, Russo A . Receptor activator of NF-kB (RANK) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients. PLoS One. 2011; 6(4):e19234. PMC: 3084800. DOI: 10.1371/journal.pone.0019234. View

Aruga A, Koizumi M, Hotta R, Takahashi S, Ogata E . Usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastasis from lung cancer. Br J Cancer. 1997; 76(6):760-4. PMC: 2228042. DOI: 10.1038/bjc.1997.458. View

Chiu Y, Tu H, Wang I, Wu C, Chang K, Liu T . The implication of osteopontin (OPN) expression and genetic polymorphisms of OPN promoter in oral carcinogenesis. Oral Oncol. 2010; 46(4):302-6. DOI: 10.1016/j.oraloncology.2010.01.018. View

Pathi S, Kowalczewski C, Tadipatri R, Fischbach C . A novel 3-D mineralized tumor model to study breast cancer bone metastasis. PLoS One. 2010; 5(1):e8849. PMC: 2809751. DOI: 10.1371/journal.pone.0008849. View

Chung J, Park M, Kim Y, Chang J, Kim J, Kim S . Usefulness of bone metabolic markers in the diagnosis of bone metastasis from lung cancer. Yonsei Med J. 2005; 46(3):388-93. PMC: 2815816. DOI: 10.3349/ymj.2005.46.3.388. View

Gandara D, Narayan S, Lara Jr P, Goldberg Z, Davies A, Lau D . Integration of novel therapeutics into combined modality therapy of locally advanced non-small cell lung cancer. Clin Cancer Res. 2005; 11(13 Pt 2):5057s-5062s. DOI: 10.1158/1078-0432.CCR-05-9012. View

Iwasaki H, Shinohara Y, Ezura Y, Ishida R, Kodaira M, Kajita M . Thirteen single-nucleotide polymorphisms in the human osteopontin gene identified by sequencing of the entire gene in Japanese individuals. J Hum Genet. 2001; 46(9):544-6. DOI: 10.1007/s100380170037. View

10.

Jin Y, Tong D, Tang L, Chen J, Zhou J, Feng Z . Expressions of Osteopontin (OPN), ανβ3 and Pim-1 Associated with Poor Prognosis in Non-small Cell Lung Cancer (NSCLC). Chin J Cancer Res. 2013; 24(2):103-8. PMC: 3555265. DOI: 10.1007/s11670-012-0103-1. View

11.

Shen H, Li Y, Liao Y, Zhang T, Liu Q, Du J . Lower blood calcium associates with unfavorable prognosis and predicts for bone metastasis in NSCLC. PLoS One. 2012; 7(3):e34264. PMC: 3316630. DOI: 10.1371/journal.pone.0034264. View

12.

Vetrone S, Montecino-Rodriguez E, Kudryashova E, Kramerova I, Hoffman E, Liu S . Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-beta. J Clin Invest. 2009; 119(6):1583-94. PMC: 2689112. DOI: 10.1172/JCI37662. View

13.

Chu M, Yang P, Hu R, Hou S, Li F, Chen Y . Elevated serum osteopontin levels and genetic polymorphisms of osteopontin are associated with Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2011; 52(10):7084-9. DOI: 10.1167/iovs.11-7539. View

14.

Schultz J, Lorenz P, Ibrahim S, Kundt G, Gross G, Kunz M . The functional -443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor. Mol Carcinog. 2008; 48(1):14-23. DOI: 10.1002/mc.20452. View

15.

Staal A, van Wijnen A, BIRKENHAGER J, Pols H, Prahl J, Deluca H . Distinct conformations of vitamin D receptor/retinoid X receptor-alpha heterodimers are specified by dinucleotide differences in the vitamin D-responsive elements of the osteocalcin and osteopontin genes. Mol Endocrinol. 1996; 10(11):1444-56. DOI: 10.1210/mend.10.11.8923469. View

16.

Senger D, Perruzzi C . Secreted phosphoprotein markers for neoplastic transformation of human epithelial and fibroblastic cells. Cancer Res. 1985; 45(11 Pt 2):5818-23. View

17.

Hashisako M, Wakamatsu K, Ikegame S, Kumazoe H, Nagata N, Kajiki A . Flare phenomenon following gefitinib treatment of lung adenocarcinoma with bone metastasis. Tohoku J Exp Med. 2012; 228(2):163-8. DOI: 10.1620/tjem.228.163. View

18.

Uaesoontrachoon K, Yoo H, Tudor E, Pike R, Mackie E, Pagel C . Osteopontin and skeletal muscle myoblasts: association with muscle regeneration and regulation of myoblast function in vitro. Int J Biochem Cell Biol. 2008; 40(10):2303-14. DOI: 10.1016/j.biocel.2008.03.020. View

19.

Clezardin P, Teti A . Bone metastasis: pathogenesis and therapeutic implications. Clin Exp Metastasis. 2007; 24(8):599-608. DOI: 10.1007/s10585-007-9112-8. View

20.

Wu C, Wu M, Chiang E, Wu C, Chen Y, Chen C . Elevated plasma osteopontin associated with gastric cancer development, invasion and survival. Gut. 2006; 56(6):782-9. PMC: 1954839. DOI: 10.1136/gut.2006.109868. View