• 福建醫(yī)科大學(xué)附屬協(xié)和醫(yī)院普外科（福建福州 350001）;

目的探討細胞內(nèi)氯離子通道蛋白1（CLIC1）蛋白在結(jié)直腸正常黏膜、腺瘤及癌組織中的差異性表達及其與結(jié)直腸癌發(fā)生、發(fā)展和預(yù)后的關(guān)系。方法采用免疫組化組織芯片方法檢測150例結(jié)直腸正常黏膜組織、62例結(jié)直腸腺瘤組織以及187例結(jié)直腸癌組織中的CLIC1蛋白表達情況，并分析CLIC1蛋白表達與結(jié)直腸癌臨床病理因素及預(yù)后的關(guān)系。結(jié)果CLIC1蛋白在結(jié)直腸正常黏膜組織（26.00%，39/150）、腺瘤組織（66.13%，41/62）和癌組織（82.89%，155/187）中的表達陽性率依次升高，之間的差異均有統(tǒng)計學(xué)意義（P lt;0.001）。 CLIC1蛋白表達與結(jié)直腸癌的TNM分期有關(guān)（P=0.007），而與患者性別（P=0.553）、年齡（P=0.206）、腫瘤直徑（P=0.185）、腫瘤分化程度（P=0.062）及腫瘤部位（P=0.598）均無關(guān)。 CLIC1蛋白陽性表達者術(shù)后中位生存時間為80個月，CLIC1陰性表達者術(shù)后中位生存時間為111個月。 log-rank檢驗表明，CLIC1蛋白陽性表達患者生存率（66.40%）明顯低于陰性表達者（80.00%），P=0.031。 結(jié)論CLIC1蛋白表達與結(jié)直腸癌的發(fā)生、發(fā)展及預(yù)后有關(guān)，CLIC1可能是一個潛在的腫瘤標(biāo)志物。

引用本文： 楊小松,池畔. 細胞內(nèi)氯離子通道蛋白1蛋白表達與結(jié)直腸癌發(fā)生、發(fā)展及預(yù)后的關(guān)系. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(7): 745-749. doi: 復(fù)制

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009 [J]. CA Cancer J Clin, 2009, 59(4): 225249.
2. Waliszewski P. Controversies about the genetic model of colorectal tumorigenesis [J]. Pol J Pathol, 1995, 46(4): 239243.
3. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis [J]. Cell, 1990, 61(5): 759767.
4. Ilyas M, Straub J, Tomlinson IP, et al. Genetic pathways in colorectal and other cancers [J]. Eur J Cancer, 1999, 35(14): 19862002.
5. Ulmasov B, Bruno J, Woost PG, et al. Tissue and subcellular distribution of CLIC1 [J]. BMC Cell Biol, 2007, 8: 8.
6. Chang YH, Wu CC, Chang KP, et al. Cell secretome analysis using hollow fiber culture system leads to the discovery of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma [J]. J Proteome Res, 2009, 8(12): 54655474.
7. Chen CD, Wang CS, Huang YH, et al. Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance [J]. Proteomics, 2007, 7(1): 155167.
8. Wang JW, Peng SY, Li JT, et al. Identification of metastasisassociated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1 [J]. Cancer Lett, 2009, 281(1): 7181.
9. Petrova DT, Asif AR, Armstrong VW, et al. Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer [J]. Clin Biochem, 2008, 41(1415): 12241236.
10. 李榮寬, 唐建武, 張軍, 等. 胞內(nèi)氯離子通道蛋白1基因沉默對小鼠肝癌細胞株增殖及侵襲能力的影響 [J]. 中華肝臟病雜志, 2010, 18(2): 131135.
11. Edge SB, Byrd DR, Compton CC, et al. eds. AJCC Cancer Staging Manual [M]. 7th ed. New York, Springer, 2010: 143164.
12. Luo J, Zha S, Gage WR, et al. AlphamethylacylCoA racemase: a new molecular marker for prostate cancer [J]. Cancer Res, 2002, 62(8): 22202226.
13. Qiu MR, Jiang L, Matthaei KI, et al. Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene [J]. Genesis, 2010, 48(2): 127136.
14. Berry KL, Hobert O. Mapping functional domains of chloride intracellular channel (CLIC) proteins in vivo [J]. J Mol Biol, 2006, 359(5): 13161333.
15. Stoychev SH, Nathaniel C, Fanucchi S, et al. Structural dynamics of soluble chloride intracellular channel protein CLIC1 examined by amide hydrogendeuterium exchange mass spectrometry [J]. Biochemistry, 2009, 48(35): 84138421.
16. Littler DR, Harrop SJ, Fairlie WD, et al. The intracellular chloride ion channel protein CLIC1 undergoes a redoxcontrolled structural transition [J]. J Biol Chem, 2004, 279(10): 92989305.
17. Kim JS, Chang JW, Yun HS, et al. Chloride intracellular channel 1 identified using proteomic analysis plays an important role in the radiosensitivity of HEp2 cells via reactive oxygen species production [J]. Proteomics, 2010, 10(14): 25892604.
18. Goodchild SC, Howell MW, Cordina NM, et al. Oxidation promotes insertion of the CLIC1 chloride intracellular channel into the membrane [J]. Eur Biophys J, 2009, 39(1): 129138.
19. Singh H, Ashley RH. Redox regulation of CLIC1 by cysteine residues associated with the putative channel pore [J]. Biophys J, 2006, 90(5): 16281638.
20. Averaimo S, Milton RH, Duchen MR, et al. Chloride intracellular channel 1 (CLIC1): sensor and effector during oxidative stress [J]. FEBS Lett, 2010, 584(10): 20762084.
21. Behrend L, Henderson G, Zwacka RM. Reactive oxygen species in oncogenic transformation [J]. Biochem Soc Trans, 2003, 31(Pt 6): 14411444.
22. Wu WS. The signaling mechanism of ROS in tumor progression [J]. Cancer Metastasis Rev, 2006, 25(4): 695705.
23. Valenzuela SM, Mazzanti M, Tonini R, et al. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle [J]. J Physiol, 2000, 529(Pt 3): 541552.
24. Sun HJ, Bahk YY, Choi YR, et al. A proteomic analysis during serial subculture and osteogenic differentiation of human mesenchymal stem cell [J]. J Orthop Res, 2006, 24(11): 20592071.
25. Menon SG, Goswami PC. A redox cycle within the cell cycle: ring in the old with the new [J]. Oncogene, 2007, 26(8): 11011109.
26. Paradisi S, Matteucci A, Fabrizi C, et al. Blockade of chloride intracellular ion channel 1 stimulates Abeta phagocytosis [J]. J Neurosci Res, 2008, 86(11): 24882498.
  1. 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009 [J]. CA Cancer J Clin, 2009, 59(4): 225249.
  2. 2. Waliszewski P. Controversies about the genetic model of colorectal tumorigenesis [J]. Pol J Pathol, 1995, 46(4): 239243.
  3. 3. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis [J]. Cell, 1990, 61(5): 759767.
  4. 4. Ilyas M, Straub J, Tomlinson IP, et al. Genetic pathways in colorectal and other cancers [J]. Eur J Cancer, 1999, 35(14): 19862002.
  5. 5. Ulmasov B, Bruno J, Woost PG, et al. Tissue and subcellular distribution of CLIC1 [J]. BMC Cell Biol, 2007, 8: 8.
  6. 6. Chang YH, Wu CC, Chang KP, et al. Cell secretome analysis using hollow fiber culture system leads to the discovery of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma [J]. J Proteome Res, 2009, 8(12): 54655474.
  7. 7. Chen CD, Wang CS, Huang YH, et al. Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance [J]. Proteomics, 2007, 7(1): 155167.
  8. 8. Wang JW, Peng SY, Li JT, et al. Identification of metastasisassociated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1 [J]. Cancer Lett, 2009, 281(1): 7181.
  9. 9. Petrova DT, Asif AR, Armstrong VW, et al. Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer [J]. Clin Biochem, 2008, 41(1415): 12241236.
  10. 10. 李榮寬, 唐建武, 張軍, 等. 胞內(nèi)氯離子通道蛋白1基因沉默對小鼠肝癌細胞株增殖及侵襲能力的影響 [J]. 中華肝臟病雜志, 2010, 18(2): 131135.
  11. 11. Edge SB, Byrd DR, Compton CC, et al. eds. AJCC Cancer Staging Manual [M]. 7th ed. New York, Springer, 2010: 143164.
  12. 12. Luo J, Zha S, Gage WR, et al. AlphamethylacylCoA racemase: a new molecular marker for prostate cancer [J]. Cancer Res, 2002, 62(8): 22202226.
  13. 13. Qiu MR, Jiang L, Matthaei KI, et al. Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene [J]. Genesis, 2010, 48(2): 127136.
  14. 14. Berry KL, Hobert O. Mapping functional domains of chloride intracellular channel (CLIC) proteins in vivo [J]. J Mol Biol, 2006, 359(5): 13161333.
  15. 15. Stoychev SH, Nathaniel C, Fanucchi S, et al. Structural dynamics of soluble chloride intracellular channel protein CLIC1 examined by amide hydrogendeuterium exchange mass spectrometry [J]. Biochemistry, 2009, 48(35): 84138421.
  16. 16. Littler DR, Harrop SJ, Fairlie WD, et al. The intracellular chloride ion channel protein CLIC1 undergoes a redoxcontrolled structural transition [J]. J Biol Chem, 2004, 279(10): 92989305.
  17. 17. Kim JS, Chang JW, Yun HS, et al. Chloride intracellular channel 1 identified using proteomic analysis plays an important role in the radiosensitivity of HEp2 cells via reactive oxygen species production [J]. Proteomics, 2010, 10(14): 25892604.
  18. 18. Goodchild SC, Howell MW, Cordina NM, et al. Oxidation promotes insertion of the CLIC1 chloride intracellular channel into the membrane [J]. Eur Biophys J, 2009, 39(1): 129138.
  19. 19. Singh H, Ashley RH. Redox regulation of CLIC1 by cysteine residues associated with the putative channel pore [J]. Biophys J, 2006, 90(5): 16281638.
  20. 20. Averaimo S, Milton RH, Duchen MR, et al. Chloride intracellular channel 1 (CLIC1): sensor and effector during oxidative stress [J]. FEBS Lett, 2010, 584(10): 20762084.
  21. 21. Behrend L, Henderson G, Zwacka RM. Reactive oxygen species in oncogenic transformation [J]. Biochem Soc Trans, 2003, 31(Pt 6): 14411444.
  22. 22. Wu WS. The signaling mechanism of ROS in tumor progression [J]. Cancer Metastasis Rev, 2006, 25(4): 695705.
  23. 23. Valenzuela SM, Mazzanti M, Tonini R, et al. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle [J]. J Physiol, 2000, 529(Pt 3): 541552.
  24. 24. Sun HJ, Bahk YY, Choi YR, et al. A proteomic analysis during serial subculture and osteogenic differentiation of human mesenchymal stem cell [J]. J Orthop Res, 2006, 24(11): 20592071.
  25. 25. Menon SG, Goswami PC. A redox cycle within the cell cycle: ring in the old with the new [J]. Oncogene, 2007, 26(8): 11011109.
  26. 26. Paradisi S, Matteucci A, Fabrizi C, et al. Blockade of chloride intracellular ion channel 1 stimulates Abeta phagocytosis [J]. J Neurosci Res, 2008, 86(11): 24882498.