DOI QR코드

DOI QR Code

Overexpressed Ostepontin-c as a Potential Biomarker for Esophageal Squamous Cell Carcinoma

  • Zhang, Mei-Xiang (Department of Clinical Lab, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital) ;
  • Xu, Yi-Jun (Department of Gastroenterology, Nanjing First Hospital & Nanjing Medical University First Hospital) ;
  • Zhu, Ming-Chen (Department of Clinical Lab, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital) ;
  • Yan, Feng (Department of Clinical Lab, Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital)
  • Published : 2013.12.31

Abstract

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

References

  1. Agrawal D, Chen T, Irby R, et al (2002). Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Ins, 94, 513-21. https://doi.org/10.1093/jnci/94.7.513
  2. Barry ST, Ludbrook SB, Murrison E, et al (2000). Analysis of the alpha4beta1 integrin-osteopontin interaction. Exp Cell Res, 258, 342-51. https://doi.org/10.1006/excr.2000.4941
  3. Chambers AF, Wilson SM, Kerkvliet N,et al (1996). Osteopontin expression in lung cancer. Lung Cancer, 15, 311-23. https://doi.org/10.1016/0169-5002(95)00595-1
  4. Furger KA, Allan AL, Wilson SM, et al (2003). Beta (3) integrin expression increases breast carcinoma cell responsiveness to the malignancy-enhancing effects of osteopontin. Mol Cancer Res, 1, 810-9.
  5. Gardner HA, Berse B, Senger DR (1994). Specific reduction in osteopontin synthesis by antisense rna inhibits the tumorigenicity of transformed rat1 fibroblasts. Oncogene, 9, 2321-6.
  6. He B, Mirza M, Weber GF (2006). An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene, 25, 2192-202. https://doi.org/10.1038/sj.onc.1209248
  7. Hofstetter W, Swisher SG, Correa AM, et al (2002). Treatment outcomes of resected esophageal cancer. Ann Surg, 236, 376-84; discussion 84-5. https://doi.org/10.1097/00000658-200209000-00014
  8. Ito T, Hashimoto Y, Tanaka E, et al (2006). An inducible shorthairpin rna vector against osteopontin reduces metastatic potential of human esophageal squamous cell carcinoma in vitro and in vivo. Clin Cancer Res, 12, 1308-16. https://doi.org/10.1158/1078-0432.CCR-05-1611
  9. Katagiri YU, Sleeman J, Fujii H, et al (1999). Cd44 variants but not cd44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginineglycine-aspartic acid, thereby stimulating cell motility and chemotaxis. Cancer Res, 59, 219-26.
  10. Kita Y, Natsugoe S, Okumura H, et al (2006). Expression of osteopontin in oesophageal squamous cell carcinoma. Br J Cancer, 95, 634-8. https://doi.org/10.1038/sj.bjc.6603296
  11. Lee JM, Wu MT, Lee YC, et al (2005). Association of gstp1 polymorphism and survival for esophageal cancer. Clin Cancer Res, 11, 4749-53. https://doi.org/10.1158/1078-0432.CCR-04-2333
  12. Lin JY, Wang MS, Dong LP, et al (2012). Influence of personal character on quality of life of patients with esophageal cancer in north Henan province and influencing factors. Asian Pac J Cancer Prev, 13, 5415-20. https://doi.org/10.7314/APJCP.2012.13.11.5415
  13. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative pcr and the 2 (-delta delta c (t)) method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  14. Ma JB, Chen EC, Song YP, et al (2013). Prognostic significance of 18F-fluorodeoxyglucose positron emission tomography (PET)-based parameters in neoadjuvant chemoradiation treatment of esophageal carcinoma. Asian Pac J Cancer Prev, 14, 2477-81. https://doi.org/10.7314/APJCP.2013.14.4.2477
  15. Mirza M, Shaughnessy E, Hurley JK, et al (2008). Osteopontin-c is a selective marker of breast cancer. Int J Cancer, 122, 889-97. https://doi.org/10.1002/ijc.23204
  16. Schorge JO, Drake RD, Lee H, et al (2004). Osteopontin as an adjunct to ca125 in detecting recurrent ovarian cancer. Clin Cancer Res, 10, 3474-8. https://doi.org/10.1158/1078-0432.CCR-03-0365
  17. Senger DR, Ledbetter SR, Claffey KP, et al (1996). Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am J Pathol, 149, 293-305.
  18. Sodek J, Ganss B, McKee MD (2000). Osteopontin. Crit Rev Oral Biol Med, 11, 279-303. https://doi.org/10.1177/10454411000110030101
  19. Thalmann GN, Sikes RA, Devoll RE, et al (1999). Osteopontin: Possible role in prostate cancer progression. Clin Cancer Res, 5, 2271-7.
  20. Tuck AB, Chambers AF (2001). The role of osteopontin in breast cancer: Clinical and experimental studies. J Mammary Gland Biol Neoplasia, 6, 419-29. https://doi.org/10.1023/A:1014734930781
  21. Vizcaino AP, Moreno V, Lambert R, et al (2002). Time trends incidence of both major histologic types of esophageal carcinomas in selected countries. Int J Cancer, 99, 860-8. https://doi.org/10.1002/ijc.10427
  22. Wang S, Liu H, Akhtar J, et al (2013). Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention. Asian Pac J Cancer Prev, 14, 5427-33. https://doi.org/10.7314/APJCP.2013.14.9.5427
  23. Weber GF, Ashkar S, Glimcher MJ, et al (1996). Receptor-ligand interaction between cd44 and osteopontin (eta-1). Science, 271, 509-12. https://doi.org/10.1126/science.271.5248.509
  24. Ye QH, Qin LX, Forgues M, et al (2003). Predicting hepatitis b virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med, 9, 416-23. https://doi.org/10.1038/nm843

Cited by

  1. Alternative Messenger RNA Splicing of Autophagic Gene Beclin 1 in Human B-cell Acute Lymphoblastic Leukemia Cells vol.15, pp.5, 2014, https://doi.org/10.7314/APJCP.2014.15.5.2153
  2. Human osteopontin: Potential clinical applications in cancer (Review) vol.39, pp.6, 2017, https://doi.org/10.3892/ijmm.2017.2964
  3. Nuclear osteopontin-c is a prognostic breast cancer marker vol.112, pp.4, 2015, https://doi.org/10.1038/bjc.2014.664
  4. Osteopontin Expression Is Associated with the Poor Prognosis in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/9098215