Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions.
Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions.
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DOI：
10.1371/journal.pone.0258878
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Baron JA
中科院分区：
文献类型：
--
作者：
Figueiredo JC;Passarelli MN;Wei W;Ahnen DJ;Morris JS;Corley L;Mehta T;Bartley AN;McKeown-Eyssen G;Bresalier RS;Barry EL;Goel A;Hernandez Mesa G;Hamilton SR;Baron JA
腺瘤和锯齿状病变代表结直肠中具有不同恶性潜能的异质早期前体组。它们通常通过组织病理学差异来区分，但人们对上皮增殖和凋亡调节的潜在差异知之甚少。我们使用 625 个结直肠腺瘤和 142 个锯齿状病变的组织微阵列进行了蛋白质表达分析，以确定上皮增殖和凋亡调节的潜在差异。我们用 Ki-67 定量增殖；活化的 caspase-3 (CASP3) 导致细胞凋亡；细胞周期蛋白 D1、p16INK2 和 p21Cip1 增殖的上调和下调调节剂；以及 BAX、BCL2 和 survivin 等凋亡调节剂。使用线性混合效应模型和circos图来确定表达和病变特征之间的关系。腺瘤的 CASP-3 标记指数 (LI) 显着高于锯齿状病变，导致净生长比较低（Ki-67 LI/激活的 CASP-3 LI，p 值<0.0001）。与锯齿状病变相比，腺瘤中的 Cyclin D1 LI、p16 LI 和 p21 LI 较低，而 BCL2 和 BAX 的表达较高 (p <0.001)。在腺瘤中，细胞周期蛋白 D1 LI 和 p16 LI 水平随着绒毛成分的增加而增加，并且在大于 2 cm 的腺瘤中检测到最高的 BAX 表达（均 p<0.0001）。右侧腺瘤的 CASP3 LI 高于左侧结直肠腺瘤 (p = 0.008)。在锯齿状病变的组织病理学亚型中，还观察到细胞周期蛋白 D1 LI、p21 LI 和生存素 LI 的显着差异。我们的研究结果表明，腺瘤中的调节蛋白表达模式与锯齿状病变不同，特别是涉及细胞凋亡。 ClinicalTrials.gov 标识符：NCT00272324
Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis. ClinicalTrials.gov Identifier: NCT00272324
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DOI：
10.1007/s00432-003-0478-y
发表时间：
2003-08-01
影响因子：
3.6
作者：
Mitomi, H;Sada, M;Otani, Y
通讯作者：
Otani, Y
影响因子：
1.9
作者：
Oka, S;Tanaka, S;Chayama, K
通讯作者：
Chayama, K
影响因子：
29.4
作者：
Gupta S;Lieberman D;Anderson JC;Burke CA;Dominitz JA;Kaltenbach T;Robertson DJ;Shaukat A;Syngal S;Rex DK
通讯作者：
Rex DK
影响因子：
7.3
作者：
Duan, WR;Garner, DS;Blomme, EAG
通讯作者：
Blomme, EAG
影响因子：
7.5
作者：
Bettington, Mark L.;Walker, Neal I.;Whitehall, Vicki L. J.
通讯作者：
Whitehall, Vicki L. J.