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The Efficacy Evaluation of Cryosurgery in Pancreatic Cancer Patients with the Expression of CD44v6, Integrin-β1, CA199, and CEA

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Abstract

Increased expression of cell adhesion molecule CD44v6, integrin-β1, carbohydrate antigen 199 (CA199), and carcinoembryonic antigen (CEA) are closely associated with the progression and metastasis of numerous cancers. In this study, peripheral blood mononuclear cell (PBMC) and serum samples were collected from 37 pancreatic cancer patients and 12 healthy people. A novel triplex TaqMan real-time reverse transcription polymerase chain reaction assay was used to measure the expression levels of CD44v6 and integrin-β1 gene in PBMCs, while chemiluminescence and enzyme-linked immunosorbent assay were used to measure the levels of CA199 and CEA expression in serum. The results showed that both the levels of CD44v6 and integrin-β1 expression had significant correlation with clinical stage, lymph node, and liver metastasis of pancreatic cancer (P < 0.05). Age, tumor size, tumor differentiation, clinical stage, lymph nodes, and liver metastasis were significantly associated with the levels of CA199 and CEA expression (P < 0.05). The levels of CD44v6, integrin-β1, CA199, and CEA expression in the patients prior cryosurgery and chemotherapy were significantly higher than those in the control group (P < 0.05), whereas no significant difference was found between the patients 1 month post cryosurgery and control group (P > 0.05). The expression levels of CD44v6, integrin-β1, CA199, and CEA in the patients 1 month post cryosurgery were significantly lower than those in the patients prior cryosurgery (P < 0.05). Interestingly, no significant difference was found for the CD44v6, integrin-β1, CA199, and CEA levels between the patients prior and post-chemotherapy (P > 0.05). The higher expression of CD44v6, integrin-β1, CA199, and CEA are closely related to the progression and metastasis of pancreatic cancer and may play a important role in the curative evaluation of cryosurgery of pancreatic cancer.

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References

  1. Hirata, K., Egawa, S., & Kimura, Y. (2007). Current status of surgery for pancreatic cancer. Digestive Surgery, 24(3), 137–141.

    Article  Google Scholar 

  2. Carpelan, M., & Nordling, S. (2005). Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut, 54(23), 385–387.

    Article  Google Scholar 

  3. Wagner, M., Redaelli, C., Lietz, M., et al. (2008). Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. British Journal of Surgery, 99(23), 586–589.

    Google Scholar 

  4. Jemal, A., Siegel, R., Ward, E., et al. (2009). Cancer statistics. CA: A Cancer Journal for Clinicians, 59(34), 225–229.

    Article  Google Scholar 

  5. Ryu, J. K., Hong, S. M., Karikari, C. A., et al. (2010). Aberrant MicroRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma. Pancreatology, 10(7), 66–73.

    Article  CAS  Google Scholar 

  6. Hynes, R. O. (1992). Integrins: versatility, modulation, and signaling in cell adhesion. Cell, 69(18), 11–17.

    Article  CAS  Google Scholar 

  7. Gu, H., Ni, C., & Zhan, R. (2000). The expression of CD15 mRNA CD44v6 mRNA and nm23H1 mRNA in breast cancer and their clinical significance. Zhonghua Yixue Zazhi, 80(12), 854–857.

    CAS  Google Scholar 

  8. Weber, G. F., Bronston, R. T., & Ilagan, J. (2002). Absence of the CD44 gene prevents sarcoma metastasis. Cancer Research, 62(56), 2281–2286.

    CAS  Google Scholar 

  9. Wang, F. L., & Wei, L. X. (2001). Expression of CD44 variant exon 6 in lung cancers. Zhongguo YixueKexueyuan Xuebao, 23(45), 401–402.

    CAS  Google Scholar 

  10. Ylagan, L. R., Scholes, J., Demopoulos, R., et al. (2000). Cd44: a marker of squamous differentiation in adenosquamous neoplasms. Archives of Pathology and Laboratory Medicine, 124(24), 212–215.

    CAS  Google Scholar 

  11. Shimabukuro, K., Toyama-Sorimachi, N., Ozaki, Y., et al. (1997). The expression patterns of standard and variant CD44 molecules in normal uterine cervix and cervical cancer. Gynecologic Oncology, 64(33), 26–34.

    Article  CAS  Google Scholar 

  12. Jing, K., Qin, S., Zhi, L., et al. (2006). Expression of E-selectin, integrin-β1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance. World J Gastroenterology, 12(2), 3609–3611.

    Google Scholar 

  13. Yao, E. S., Zhang, H., Chen, Y. Y., et al. (2007). Increased beta1 integrin is associated with decreased survival in invasive breast cancer. Cancer Research, 67(42), 659–664.

    Article  CAS  Google Scholar 

  14. Yang, G. Y., Xu, K. S., Pan, Z. Q., et al. (2008). Integrin α-β6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver. Cancer Science, 99(9), 879–887.

    Article  CAS  Google Scholar 

  15. Wagner, M., Redaelli, C., & Lietz, M. (2008). Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. British Journal of Surgery, 86(12), 586–890.

    Google Scholar 

  16. Okusaka, T., Funakoshi, A., Furuse, J., et al. (2007). A late phase II study of S1 for metastatic pancreatic cancer. Cancer Chemotherapy and Pharmacology, 87(123), 578–582.

    Google Scholar 

  17. Yamazaki, H., Nishiyama, K., Koizumi, M., et al. (2007). Chemoradiotherapy for adcanced pancreatic cancer gemcitabine can be administered using limited-field radiotherapy. Strahlentherapie und Onkologie, 183(27), 301–306.

    Article  Google Scholar 

  18. Xu, K. C., & Niu, L. Z. (2003). Percutaneous cryoablation in combination with ethanol injection for unresectable hepatocellular carcinoma. World Journal of Gastroenterology, 59(37), 2686–2689.

    Google Scholar 

  19. Mouraviev, V., & Polascik, T. J. (2006). Update on cryotherapy for prostate cancer. Current Opinion in Urology, 16(67), 152–156.

    Article  Google Scholar 

  20. Xu, K. C., & Niu, L. Z. (2003). Sequential treatment of transarterial chemoembolization percutaneous cryoablation for unresectable primary liver cancer. World Journal of Gastroenterology, 9(29), 2688–2691.

    Google Scholar 

  21. Rautava, J., Soukka, T., Inki, P., et al. (2003). CD44v6 in developing, dysplastic and malignant oral epithelia. Oral Oncology, 39(33), 373–379.

    Article  CAS  Google Scholar 

  22. Cheresh, D. A. (1992). Strucural and biologic properties of integrinmediated cell adhesion. Clinics in Laboratory Medicine, 12(9), 217–219.

    CAS  Google Scholar 

  23. Vizoso, F. J., Fernández, J. C., Corte, M. D., et al. (2004). Expression and clinical significance of CD44v5 and CD44v6 in resectable colorectal cancer. Journal of Cancer Research and Clinical Oncology, 130(35), 679–680.

    Article  Google Scholar 

  24. Yamamichi, K., Uehara, Y., & Kitamura, N. (1998). Increased expression of CD44v6 mRNA significantly correlates with distant metastasis and poor prognosis in gastric cancer. Cancer, 79(17), 256–262.

    CAS  Google Scholar 

  25. Fasano, M., & Sabatini, M. T. (1997). CD44 and its v6 spliced variant in lung tumors: A role in histogenesis. Cancer, 88(18), 34–41.

    Article  Google Scholar 

  26. Pignatelli, M., Hanby, A. M., & Stamp, G. W. (1991). Low expression of beta1, alpha2 and alpha3 subunits of VLA integrins in malignant mammary tumours. Journal of Pathology, 165(45), 25–32.

    Article  CAS  Google Scholar 

  27. Eble, J. A., & Haier, J. (2006). Integrins in cancer treatment. Curr Cancer Drug Target, 6(19), 89–95.

    Article  CAS  Google Scholar 

  28. Klatte, T., Seligson, D. B., & Rao, J. Y. (2010). Absent CD44v6 expression is an independent predictor of poor urothelial bladder cancer outcome. Journal of Urology, 83(66), 2403–2408.

    Article  Google Scholar 

  29. Saito, H., Tsujitani, S., Katano, K., et al. (1998). Serum concentration of CD44 variant 6 and its relation to prognosis in patients with gastric carcinoma. Cancer, 83(7), 1094–1098.

    Article  CAS  Google Scholar 

  30. Miyoshi, T., & Konda, K. (1997). The expression of the CD44 variant exon6 is associated with lymph node metastasis in non-small cell lung cancer. Clinical Cancer Research, 3(10), 1289–1292.

    CAS  Google Scholar 

  31. Du, Y., Yang, C., Zhang, X., et al. (2008). Expression and significance of integrin beta1 and integrin-linked kinase in laryngeal carcinoma. Lin Chuang Er Bi Yan Hou Jing Wai Ke Za Zhi, 22(23), 500–503.

    Google Scholar 

  32. Chi, F., & Wang, Z. (2010). Expression of integrin beta1 in human gastric cardia adenocarcinoma tissues and their correlations with clinicalpathological significance. Chin J Cancer Prev Treat, 17(27), 752–754.

    CAS  Google Scholar 

  33. Park, C. C., Zhang, H., Pallavicini, M., et al. (2006). Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Research, 66(22), 15–26.

    Google Scholar 

  34. Klatte, T., Seligson, D. B., Rao, J. Y., et al. (2010). Absent CD44v6 expression is an independent predictor of poor urothelial bladder cancer outcome. Journal of Urology, 183(22), 2403–2408.

    Article  CAS  Google Scholar 

  35. Saito, H., & Tsujitani, S. (1998). Serum concentration of CD44 variant 6 and its relation to prognosis in patients with gastric carcinoma. Cancer, 83(112), 1094–1098.

    Article  CAS  Google Scholar 

  36. Ju, L., Zhou, C., & Li, W. (2009). Effect of integrin β1 up-regulation on the migration and adhesion capacity of lung cancer cell. Progress in Modern Biomedicine, 9(29), 3807–3812.

    CAS  Google Scholar 

  37. Zhang, Y. (2005). The relation between CD44 and tumor development. Journal of Chinese Medical, 22(56), 343–346.

    Google Scholar 

  38. Kang, C. M., Kim, J. Y., Choi, G. H., et al. (2007). The use of adjusted preoperative CA19–9 to predict the recurrence of resectable pancreatic cancer. Journal of Surgical Research, 140(1), 31–35.

    Article  CAS  Google Scholar 

  39. Giannini, E., Borro, P., Botta, F., et al. (2001). Cholestasis is the main determinant of abnormal CA199 levels in patients with pancreatic cancer. International Journal of Biological Markers, 15(55), 126–129.

    Google Scholar 

  40. Jiang, J. T., Wu, C. P., Deng, H. F., et al. (2004). Serum Level of CEA, CA242 and CA199 in pancreatic cancer. World Journal of Gastroenterology, 10(11), 1675–1679.

    CAS  Google Scholar 

  41. Kovach, S. J., & Hendrickson, R. J. (2002). Cryoablation of unresectable pancreatic cancer. Surgery, 131(31), 463–465.

    Article  Google Scholar 

  42. Korpan, N. N. (2001). Pancreas cryosurgery. In N. N. Korpan (Ed.), Basics of Cryosurgery (1st ed.). Wein, NY: Springer-Verlag.

    Google Scholar 

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Acknowledgments

We would like to express appreciation to Xiaopeng Liu, Zhiju Zhao, Chengqian Feng, and Mengtian Liao for processing clinical samples. The authors also thank the assistance of all medical and nursing staff of Fuda Cancer Hospital who cared for the patients in the study.

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Correspondence to Kecheng Xu.

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Zhou, G., Chiu, D., Qin, D. et al. The Efficacy Evaluation of Cryosurgery in Pancreatic Cancer Patients with the Expression of CD44v6, Integrin-β1, CA199, and CEA. Mol Biotechnol 52, 59–67 (2012). https://doi.org/10.1007/s12033-011-9474-7

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  • DOI: https://doi.org/10.1007/s12033-011-9474-7

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