• 西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院肝膽外科（西安 710061）;

目的　 檢測胰腺癌組織中的 CXCR4 和β-catenin的表達，并探討兩者的相互關(guān)系及其在胰腺癌侵襲和轉(zhuǎn)移中的臨床意義。
方法 　應(yīng)用免疫組化SP法對48例胰腺癌及20例正常胰腺組織中的CXCR4和　β-catenin 蛋白進行檢測，并結(jié)合臨床資料進行分析，采用Kaplan-Meier法分析目標蛋白的表達與臨床預(yù)后的關(guān)系，2組間的生存率曲線比較的假設(shè)檢驗采用Log-rank法； 多因素分析采用Cox比例風(fēng)險回歸模型。
結(jié)果 　CXCR4與β-catenin在胰腺癌組織中的表達陽性率分別為85.4%(41/48)和75.0%(36/48)。CXCR4與β-catenin的共表達率為70.8%（34/48）。CXCR4的陽性表達與淋巴結(jié)轉(zhuǎn)移、TNM分期有關(guān)（P值分別為0.012、0.005），β-catenin的陽性表達與淋巴結(jié)轉(zhuǎn)移有關(guān)(P=0.047)。Kaplan-Meier生存曲線提示CXCR4陽性表達是胰腺癌預(yù)后差的一個指標。Cox多因素方差分析提示CXCR4、TNM分期、淋巴結(jié)轉(zhuǎn)移是影響胰腺癌預(yù)后的獨立因素。
結(jié)論 　胰腺癌中　CXCR4 及β-catenin均異常表達，與胰腺癌的生物學(xué)效應(yīng)密切相關(guān)； CXCR4的異常表達可能是胰腺癌侵襲、轉(zhuǎn)移的分子機理之一。

引用本文： 王錚,馬清涌,李軍輝,劉青光. CXCR4和β-catenin在胰腺癌組織中的表達及其臨床意義. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(10): 1071-1076. doi: 復(fù)制

1. 　趙玉沛. 胰腺癌診斷與治療的現(xiàn)狀與未來 [J]. 中華肝膽外科雜志， 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.
  1. 1. 　趙玉沛. 胰腺癌診斷與治療的現(xiàn)狀與未來 [J]. 中華肝膽外科雜志， 2009; 15(5): 321-324.
  2. 2. 　Soon LL. A discourse on cancer cell chemotaxis: where to from here? [J]. IUBMB Life, 2007; 59(2): 60-67.
  3. 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. 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. 5. 　Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009 [J]. CA Cancer J Clin, 2009; 59(4): 229-249.
  6. 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. 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. 8. 　Balkwill F. Cancer and the chemokine network [J]. Nat Rev Cancer, 2004; 4(7): 540-550.
  9. 9. 　Busillo JM, Benovic JL. Regulation of CXCR4 signaling [J]. Biochim Biophys Acta, 2007; 1768(4): 952-963.
  10. 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. 11. 　Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4 [J]. Semin Cancer Biol, 2004; 14(3): 171-179.
  12. 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. 13. 　Luker KE, Luker GD. Functions of CXCL12 and CXCR4 in breast cancer [J]. Cancer Lett, 2006; 238(1): 30-41.
  14. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 25. 　Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited [J]. Nat Rev Cancer, 2003; 3(6): 453-458.