Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
BMC Cancer. 2010 Feb 10;10:38. doi: 10.1186/1471-2407-10-38.
Although Argonaute proteins are considered to play important roles in stem cell self-renewal, RNA interference (RNAi) and translational regulation, relatively little is known about their functions in human disease. In this study, we investigated the expression of eight members of human Argonaute family in colon cancer and identified their potential roles in tumor development and progression.
Antibodies against human Argonaute proteins were prepared by immunizing rabbits with synthetic peptides derived from the sequences of Argonaute members. Then we constructed a tissue microarray containing 75 specimens from colon cancer and 75 specimens from adjacent non-cancer tissue, and assayed eight different proteins (EIF2C1, EIF2C2, EIF2C3, EIF2C4, PIWIL1, PIWIL2, PIWIL3 and PIWIL4) by immunohistochemistry on consecutive formalin-fixed tissue microarray sections.
The expression of EIF2C1-4 and PIWIL1-4 was significantly higher in tumorous tissue than in adjacent tissue. Notably, a significant correlation was observed between the positive expression of EIF2C2, EIF2C3, EIF2C4, PIWIL4 and the presence of distant metastasis. Logistic regression analysis revealed that an increased expression of EIF2C1 and PIWIL2 was significantly associated with occurrence of colon cancer tissue compared with non-cancer tissue.
Argonaute proteins are overexpressed in colon cancer relative to adjacent non-cancer tissue. The expression of EIF2C2-4 and PIWIL4 appears increased in advanced tumors with distant metastasis, suggesting it may promote tumor invasion. Furthermore, EIF2C1 and PIWIL2 might represent novel colon cancer markers with early diagnostic significance.
Argonaute 蛋白被认为在干细胞自我更新、RNA 干扰 (RNAi) 和翻译调控中发挥重要作用，但它们在人类疾病中的功能相对知之甚少。在这项研究中，我们研究了人 Argonaute 家族的 8 个成员在结肠癌中的表达，并鉴定了它们在肿瘤发生和发展中的潜在作用。
通过用合成肽免疫兔子制备了针对人 Argonaute 蛋白的抗体，这些肽源自 Argonaute 成员的序列。然后，我们构建了一个组织微阵列，其中包含 75 例结肠癌标本和 75 例癌旁非肿瘤组织标本，并通过免疫组织化学方法在连续的福尔马林固定组织微阵列切片上检测了 8 种不同的蛋白质 (EIF2C1、EIF2C2、EIF2C3、EIF2C4、PIWIL1、PIWIL2、PIWIL3 和 PIWIL4)。
EIF2C1-4 和 PIWIL1-4 在肿瘤组织中的表达明显高于癌旁组织。值得注意的是，EIF2C2、EIF2C3、EIF2C4、PIWIL4 的阳性表达与远处转移的存在之间存在显著相关性。逻辑回归分析显示，与非肿瘤组织相比，EIF2C1 和 PIWIL2 的高表达与结肠癌组织的发生显著相关。
Argonaute 蛋白在结肠癌中相对于癌旁非肿瘤组织表达上调。EIF2C2-4 和 PIWIL4 的表达在有远处转移的晚期肿瘤中增加，提示其可能促进肿瘤侵袭。此外，EIF2C1 和 PIWIL2 可能代表具有早期诊断意义的新型结肠癌标志物。
