Wang Ning, Chen Yang, Han Yuchen, Zhao Yue, Liu Yü, Guo Kejian, Jiang Yi
Department of General Surgery, First Hospital of China Medical University, Shenyang, China.
Tumori. 2012 Nov;98(6):783-91. doi: 10.1177/030089161209800617.
The aim of the study was to screen the markedly down-regulated proteins in colorectal cancer and analyze their relationship to carcinogenesis, cancer progression and pathological aspects.
Proteomic analysis was preformed on six fresh colorectal cancer tissues and paired normal colorectal mucosa by two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Two markedly down-regulated proteins among the proteins, of which the expressions were significantly decreased in colorectal cancer compared to normal mucosa, were confirmed by Western Blot in 12 colorectal cancers. Their relationship to carcinogenesis, cancer progression and pathological aspects of colorectal cancer were analyzed in 64 colorectal cancer and paired normal mucosa, 27 benign polyps, and 20 lymph node metastases by immunohistochemistry.
Two-dimensional differential gel electrophoresis analysis showed there were 2 protein spots, of which the average abundances decreased 3.62 and 3.76 fold in colorectal cancer compared to normal mucosa, respectively. They were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry as carbonic anhydrase I and II (CAI and CAII). Validation by Western Blot in 12 colorectal cancers showed there were significantly different expressions of CAI and CAII between colorectal cancer and normal mucosa ( P = 0.002 and 0.027, respectively). Immunohistochemistry analysis indicated the expression of CAI and CAII was decreased from normal mucosa to benign polyps, and to colorectal cancer stepwise significantly (P <0.05). However, there were no differences in their expressions between lymph node metastasis and colorectal cancer (P >0.05). There were decreasing trends of CAI and CAII expressions from well to poor differentiation and from stage I or II to stage III or IV, but they were not statistically significant (P >0.05).
CAI and CAII are necessary enzymes of the colorectum for their normal function. Down-regulations of CAI and CAII are early events of colorectum carcinogenesis. They have no correlations with lymph node metastasis.
本研究旨在筛选结直肠癌中显著下调的蛋白质，并分析它们与致癌作用、癌症进展及病理特征的关系。
采用二维差异凝胶电泳和基质辅助激光解吸/电离飞行时间质谱技术，对6例新鲜结直肠癌组织及其配对的正常结直肠黏膜进行蛋白质组学分析。在12例结直肠癌中，通过蛋白质免疫印迹法对其中2种在结直肠癌中表达明显低于正常黏膜的显著下调蛋白质进行验证。通过免疫组织化学方法，在64例结直肠癌及其配对的正常黏膜、27例良性息肉和20例淋巴结转移病例中，分析它们与结直肠癌的致癌作用,癌症进展及病理特征的关系。
二维差异凝胶电泳分析显示有2个蛋白点，其在结直肠癌中的平均丰度分别比正常黏膜降低了3.62倍和3.76倍。经基质辅助激光解吸/电离飞行时间质谱鉴定，它们分别为碳酸酐酶I和II（CAI和CAII）。蛋白质免疫印迹法在12例结直肠癌中的验证结果显示，CAI和CAII在结直肠癌和正常黏膜之间的表达存在显著差异（P值分别为0.002和0.027）。免疫组织化学分析表明，从正常黏膜到良性息肉再到结直肠癌，CAI和CAII的表达呈逐步显著下降（P<0.05）。然而，它们在淋巴结转移和结直肠癌中的表达没有差异（P>0.05）。从高分化到低分化以及从I期或II期到III期或IV期，CAI和CAII的表达呈下降趋势，但无统计学意义（P>0.05）。
CAI和CAII是结直肠正常功能所必需的酶。CAI和CAII的下调是结直肠癌发生的早期事件。它们与淋巴结转移无关。
