Expressions and Clinical Significances of CXCR4 and β-catenin in Pancreatic Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Zheng , MA Qingyong , LI Junhui , LIU Qingguang.

Department of Hepatobiliary Surgery, The First Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an 710061, ChinaCorresponding Author: LIU Qing-guang, E-mail： liuqingguang@vip.sina.com;

Corresponding author：

Keywords：

CXCR4; β-catenin; Pancreatic cancer; Tumor metastasis

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Objective 　To investigate the expressions of CXCR4 and β-catenin in pancreatic cancer, explore the relationship between them, and explore the possible biomarkers about invasion and metastasis of pancreatic cancer.
Methods 　Forty-eight samples of pancreatic cancer and 20 samples of normal pancreas tissues were selected. The expressions of CXCR4 and β-catenin were examined by the immunohistological technique. Spearman, Chi-square， and rank test were used to analyze the relation between the protein expressions and clinical characteristics. Survival analysis was evaluated by Kaplan-Meier product limit method and Log-rank test. Variables were evaluated by Cox proportional hazards analysis. The size of test was 0.05.
Results 　The positive expression rates of CXCR4 and β-catenin in pancreatic cancer tissues were 85.4% (41/48) and 75.0% (36/48), respectively. Co-expression rate of 　CXCR4 and β-catenin was 70.8% (34/48). There were significant differences between various CXCR4 staining and lymph node metastasis and TNM stage (P=0.012, 0.005, respectively). β-catenin positive expression was associated with lymph node metastasis (P=0.047). However, abnormal β-catenin positive expression could not determine the clinical survival. Kaplan-Meier estimated curves suggested that clinical prognosis was poor for patients with 　CXCR4 　expression. Multivariate analysis showed that CXCR4, late TNM stage, and lymph node metastasis were independent prognostic factors for pancreatic cancer.
Conclusions　 Both CXCR4 and 　β-catenin abnormally express in pancreatic cancer. CXCR4 may be an important marker for pancreatic cancer progression.

Citation： WANG Zheng,MA Qingyong,LI Junhui,LIU Qingguang.. Expressions and Clinical Significances of CXCR4 and β-catenin in Pancreatic Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(10): 1071-1076. doi: Copy

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1. 　赵玉沛. 胰腺癌诊断与治疗的现状与未来 [J]. 中华肝胆外科杂志， 2009; 15(5): 321-324.
2. 　Soon LL. A discourse on cancer cell chemotaxis: where to from here? [J]. IUBMB Life, 2007; 59(2): 60-67.
3. 　Kim K, Lu Z, Hay ED. Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT [J]. Cell Biol Int, 2002; 26(5): 463-476.
4. 　Leo C, Horn LC, Rauscher C, et al. Expression of erythropoietin and erythropoietin receptor in cervical cancer and relationship to survival, hypoxia, and apoptosis [J]. Clin Cancer Res, 2006; 12(23): 6894-6900.
5. 　Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009 [J]. CA Cancer J Clin, 2009; 59(4): 229-249.
6. 　Roland J, Murphy BJ, Ahr B, et al. Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling [J]. Blood, 2003; 101(2): 399-406.
7. 　Juarez J, Bendall L, Bradstock K. Chemokines and their receptors as therapeutic targets: the role of the SDF-1/CXCR4 axis [J]. Curr Pharm Des, 2004; 10(11): 1245-1259.
8. 　Balkwill F. Cancer and the chemokine network [J]. Nat Rev Cancer, 2004; 4(7): 540-550.
9. 　Busillo JM, Benovic JL. Regulation of CXCR4 signaling [J]. Biochim Biophys Acta, 2007; 1768(4): 952-963.
10. 　〖KG-*4〗Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment [J]. Blood, 2006; 107(5): 1761-1767.
11. 　Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4 [J]. Semin Cancer Biol, 2004; 14(3): 171-179.
12. 　Sasaki K, Natsugoe S, Ishigami S, et al. Expression of 　CXCL12 and its receptor CXCR4 in esophageal squamous cell carcinoma [J]. Oncol Rep, 2009; 21(1): 65-71.
13. 　Luker KE, Luker GD. Functions of CXCL12 and CXCR4 in breast cancer [J]. Cancer Lett, 2006; 238(1): 30-41.
14. 　Chen Y, Stamatoyannopoulos G, Song CZ. Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro [J]. Cancer Res, 2003; 63(16): 4801-4804.
15. 　Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression [J]. Clin Cancer Res, 2000; 6(9): 3530-3535.
16. 　Holm NT, Byrnes K, Li BD, et al. Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence [J]. J Surg Res, 2007; 141(1): 53-59.
17. 　Zeng G, Germinaro M, Micsenyi A, et al. Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma [J]. Neoplasia, 2006; 8(4): 279-289.
18. 　Ben-Zev A, Shtutman M, Zhurinsky J. The integration of cell adhesion with gene expression: the role of beta-catenin [J]. Exp Cell Res, 2000; 261(1): 75-82.
19. 　Kim K, Lu Z, Hay ED. Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT [J]. Cell Biol Int, 2002; 26(5): 463-476.
20. 　Pasca di Magliano M, Biankin AV, Heiser PW, et al. Common activation of canonical Wnt signaling in pancreatic adenocarcinoma [J]. PLoS One, 2007; 2(11): e1155.
21. 　Zeng G, Germinaro M, Micsenyi A, et al. Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma [J]. Neoplasia, 2006; 8(4): 279-289.
22. 　Pilarsky C, Ammerpohl O, Sipos B, et al. Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling [J]. J Cell Mol Med, 2008; 12(6B): 2823-2835.
23. 　Wang Z, Ma Q, Liu Q, et al. Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway [J]. Br J Cancer, 2008; 99(10): 1695-1703.
24. 　Wang Z, Ma Q. beta-Catenin is a promising key factor in the SDF-1/CXCR4 axis on metastasis of pancreatic cancer [J]. Med Hypotheses, 2007; 69(4): 816-820.
25. 　Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited [J]. Nat Rev Cancer, 2003; 3(6): 453-458.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions and Clinical Significances of CXCR4 and β-catenin in Pancreatic Cancer

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