Characterisation and protein expression profiling of annexins in colorectal cancer.
Characterisation and protein expression profiling of annexins in colorectal cancer.
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DOI：
10.1038/sj.bjc.6604128
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发表时间：
2008-01-29
影响因子：
8.8
通讯作者：
Murray, G. I.
中科院分区：
文献类型：
--
作者：
Duncan, R.;Carpenter, B.;Main, L. C.;Telfer, C.;Murray, G. I.
膜联蛋白是钙调节磷脂结合蛋白家族，在细胞生物学中具有多种作用。单个膜联蛋白与肿瘤的发展和进展有关，在这项研究中，对一系列膜联蛋白在结直肠癌中的作用进行了研究。通过比较蛋白质组学分析鉴定出膜联蛋白A1、A2、A4和A11在结直肠癌中过表达。通过免疫组化进一步研究了包含原发性和转移性结直肠癌以及正常结肠的结直肠癌组织芯片的膜联蛋白A1、A2、A4和A11。Annexins A1（P=0.01）、A2（P<0.001）、A4（P<0.001）和A11（P<0.001）在原发性结肠癌中的表达明显高于正常结肠组织。Annexins A2（P=0.001）、A4（P=0.03）和A11（P=0.006）的表达随肿瘤分期的增加而增加。通过k均值聚类分析鉴定膜联蛋白表达谱，并且膜联蛋白谱与肿瘤分期（P=0.01）以及患者存活率相关。膜联蛋白簇组1（低膜联蛋白表达）中的患者比簇组2（高膜联蛋白A4和A11表达）中的患者具有更好的存活率（对数秩=5.33，P=0.02）。总之，这项研究表明，个别膜联蛋白存在于结直肠癌中，特定的膜联蛋白在结直肠癌中过表达，膜联蛋白表达谱与生存相关。
The annexins are family of calcium-regulated phospholipid-binding proteins with diverse roles in cell biology. Individual annexins have been implicated in tumour development and progression, and in this investigation a range of annexins have been studied in colorectal cancer. Annexins A1, A2, A4 and A11 were identified by comparative proteomic analysis to be overexpressed in colorectal cancer. Annexins A1, A2, A4 and A11 were further studied by immunohistochemistry with a colorectal cancer tissue microarray containing primary and metastatic colorectal cancer and also normal colon. There was significant increase in expression in annexins A1 (P=0.01), A2 (P<0.001), A4 (P<0.001) and A11 (P<0.001) in primary tumours compared with normal colon. There was increasing expression of annexins A2 (P=0.001), A4 (P=0.03) and A11 (P=0.006) with increasing tumour stage. An annexin expression profile was identified by k-means cluster analysis, and the annexin profile was associated with tumour stage (P=0.01) and also patient survival. Patients in annexin cluster group 1 (low annexin expression) had a better survival (log rank=5.33, P=0.02) than patients in cluster group 2 (high annexins A4 and A11 expression). In conclusion, this study has shown that individual annexins are present in colorectal cancer, specific annexins are overexpressed in colorectal cancer and the annexin expression profile is associated with survival.
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