Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway
Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway
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DOI：
10.3748/wjg.v21.i33.9749
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发表时间：
2015-09-07
影响因子：
4.3
通讯作者：
Kang, Gyeong Hoon
中科院分区：
文献类型：
--
作者：
Bae, Jeong Mo;Kim, Jung Ho;Kang, Gyeong Hoon
目的：验证膜联蛋白A10作为侵袭性结直肠癌（crc）中锯齿状瘤变途径的替代标志物的实用性。方法：共纳入2004年1月至2007年12月在首尔国立大学医院接受手术切除的1133例原发性结直肠癌患者。膜联蛋白A10的表达通过组织芯片免疫组化评估，并与我们对每个个体的临床病理和分子特征的研究结果配对。甲基光法测定CpG岛甲基化表型，高效液相色谱法测定微卫星不稳定性。通过直接测序和等位基因特异性PCR评估KRAS和BRAF突变状态。通过单因素和分期特异性生存分析来揭示膜联蛋白A10表达的预后价值。结果：1133例患者中有66例（5.8%）表达Annexin A10。Annexin A10的表达多见于女性，且与近端部位、溃疡大体类型、晚期T型、N型及TNM分期有关。表达膜联蛋白A10的crc表现为没有管腔坏死、管腔窄化和粘蛋白产生。表达Annexin A10的crc与CpG岛甲基化表型、微卫星不稳定性和BRAF突变相关。在生存分析中，Annexin A10的表达与较差的总生存期和无进展生存期相关，尤其是在分期中。crc。结论：膜联蛋白A10表达与不良临床行为相关，可作为侵袭性crc中锯齿状瘤变通路的支持性替代标志物。
AIM: To validate the utility of Annexin A10 as a surrogate marker of the serrated neoplasia pathway in invasive colorectal cancers (CRCs).METHODS: A total of 1133 primary CRC patients who underwent surgical resection at Seoul National University Hospital between January 2004 and December 2007 were enrolled. Expression of Annexin A10 was evaluated by immunohistochemistry using tissue microarray and paired to our findings on clinicopathologic and molecular characteristics of each individual. CpG island methylator phenotype was determined by MethyLight assay and microsatellite instability was determined by high performance liquid chromatography. KRAS and BRAF mutation status was evaluated by direct sequencing and allele-specific PCR. Univariate and stage-specific survival analyses were performed to reveal the prognostic value of Annexin A10 expression.RESULTS: Annexin A10 expression was observed in 66 (5.8%) of the 1133 patients. Annexin A10 expression was more commonly found in females and was associated with proximal location, ulcerative gross type, advanced T category, N category and TNM stage. CRCs with Annexin A10 expression showed an absence of luminal necrosis, luminal serration and mucin production. CRCs with Annexin A10 expression were associated with CpG island methylator phenotype, microsatellite instability and BRAF mutation. In survival analysis, Annexin A10 expression was associated with poor overall survival and progression-free survival, especially in stage. CRCs.CONCLUSION: Annexin A10 expression is associated with poor clinical behavior and can be used a supportive surrogate marker of the serrated neoplasia pathway in invasive CRCs.