Expression of the antiapoptotic protein survivin in colon cancer.
Expression of the antiapoptotic protein survivin in colon cancer.
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DOI：
10.1016/j.clcc.2011.03.014
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发表时间：
2011-09
影响因子：
3.4
通讯作者：
Shibata D
中科院分区：
文献类型：
--
作者：
Hernandez JM;Farma JM;Coppola D;Hakam A;Fulp WJ;Chen DT;Siegel EM;Yeatman TJ;Shibata D
抗凋亡蛋白Survivin在结直肠癌的发生发展中起重要作用。然而，尚不清楚存活素的上调是否在疾病的进行性阶段得以维持，或者是否有其他凋亡相关基因共表达和/或被抑制。我们试图评估生存素在结肠肿瘤中的表达，并确定与其他凋亡调节因子的关系。使用GeneChip Human Genome U133 Plus 2.0 Array（Affyestival，Santa Clara，CA）分析来自168名原发性结直肠癌患者的组织样本，并评估生存素表达。在86名患者的组织微阵列（TMA）块中使用了生存素和一组凋亡相关蛋白的免疫组织化学染色;通过染色强度和阳性细胞百分比（范围，0-9）进行评分。与正常结肠组织相比，Survivin mRNA在原发性结肠癌（无论美国癌症联合委员会（AJCC）分期如何）和转移灶中均上调（1.8倍增加）（P <0.0001）。Survivin染色在93%的腺癌中呈阳性（中位免疫组化[IHC]评分：2 [范围，1-6]），100%的腺瘤中呈阳性（1 [范围，1-2]），43%的正常结肠粘膜中呈阳性（1，[范围1-2]）（P = .006）。Survivin的表达随肿瘤分级的加重而增加（P <0.05）。在结肠癌中，生存素表达与CD 45 A（P = 0.001）、TACE（P = 0.003）和MCL 1（P = 0.01）的共表达呈正相关，与BAX呈负相关趋势（P = 0.058）。Survivin的表达在正常的粘膜-腺瘤-癌序列中增加，并在疾病的整个进展过程中保持，这增强了其作为治疗靶点的吸引力。此外，我们已经证明了其他几个乳腺癌相关基因的共过表达，这反过来可能成为额外的和潜在的协同治疗靶点。
The antiapoptotic protein survivin has been demonstrated to play an important role in colorectal carcinogenesis. However it is unclear whether the upregulation of survivin is maintained through progressive stages of disease, or if other apoptosis-related genes are coexpressed and/or repressed. We sought to evaluate survivin expression in colonic neoplasia and identify relationships with additional regulators of apoptosis. Tissue samples from 168 patients with primary colorectal cancer were profiled using the GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) and evaluated for survivin expression. Immunohistochemical staining for survivin and a panel of apoptosis-associated proteins were used in 86 patients with tissue microarray (TMA) blocks; scoring was by stain intensity and percentage of positive cells (range, 0–9). Survivin mRNA was upregulated (1.8-fold increase) in primary colon cancers— irrespective of American Joint Committee on Cancer (AJCC) stage— and metastases compared with normal colonic tissue (P < .0001). Survivin staining was positive in 93% of adenocarcinomas (median immunohistochemistry [IHC] score: 2 [range, 1–6]), 100% of adenomas (1 [range,1–2]), and 43% of normal colonic mucosa (1, [range 1–2]) (P = .006). Survivin expression increased with worsening tumor grade (P < .05). In colon cancers, survivin expression positively correlated with the coexpression of PUMA (P = .001), TACE (P = .003), and MCL1 (P = .01), and trended toward an inverse correlation with BAX (P = .058). Survivin expression increases during the normal mucosa-adenoma-carcinoma sequence and is maintained throughout progression of disease, which strengthens its appeal as a therapeutic target. Furthermore, we have demonstrated co-overexpression of several other apoptosis-related genes, which may in turn serve as additional and potentially synergistic therapeutic targets.
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影响因子：
5.1
作者：
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通讯作者：
Chao, Jui-I
影响因子：
8
作者：
Islam, A;Kageyama, H;Nakagawara, A
通讯作者：
Nakagawara, A
影响因子：
45.3
作者：
Hirschowitz, EA;Foody, T;Yannelli, J
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Yannelli, J
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影响因子：
4.8
作者：
Kabra, Neha;Li, Zhenyu;Chen, Jiandong
通讯作者：
Chen, Jiandong
影响因子：
5.7
作者：
Paduano, F;Villa, R;Zaffaroni, N
通讯作者：
Zaffaroni, N