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
Hirata, K., Egawa, S., & Kimura, Y. (2007). Current status of surgery for pancreatic cancer. Digestive Surgery, 24(3), 137–141.
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.
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.
Jemal, A., Siegel, R., Ward, E., et al. (2009). Cancer statistics. CA: A Cancer Journal for Clinicians, 59(34), 225–229.
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.
Hynes, R. O. (1992). Integrins: versatility, modulation, and signaling in cell adhesion. Cell, 69(18), 11–17.
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.
Weber, G. F., Bronston, R. T., & Ilagan, J. (2002). Absence of the CD44 gene prevents sarcoma metastasis. Cancer Research, 62(56), 2281–2286.
Wang, F. L., & Wei, L. X. (2001). Expression of CD44 variant exon 6 in lung cancers. Zhongguo YixueKexueyuan Xuebao, 23(45), 401–402.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Mouraviev, V., & Polascik, T. J. (2006). Update on cryotherapy for prostate cancer. Current Opinion in Urology, 16(67), 152–156.
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.
Rautava, J., Soukka, T., Inki, P., et al. (2003). CD44v6 in developing, dysplastic and malignant oral epithelia. Oral Oncology, 39(33), 373–379.
Cheresh, D. A. (1992). Strucural and biologic properties of integrinmediated cell adhesion. Clinics in Laboratory Medicine, 12(9), 217–219.
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.
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.
Fasano, M., & Sabatini, M. T. (1997). CD44 and its v6 spliced variant in lung tumors: A role in histogenesis. Cancer, 88(18), 34–41.
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.
Eble, J. A., & Haier, J. (2006). Integrins in cancer treatment. Curr Cancer Drug Target, 6(19), 89–95.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Zhang, Y. (2005). The relation between CD44 and tumor development. Journal of Chinese Medical, 22(56), 343–346.
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.
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.
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.
Kovach, S. J., & Hendrickson, R. J. (2002). Cryoablation of unresectable pancreatic cancer. Surgery, 131(31), 463–465.
Korpan, N. N. (2001). Pancreas cryosurgery. In N. N. Korpan (Ed.), Basics of Cryosurgery (1st ed.). Wein, NY: Springer-Verlag.
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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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