First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
BMC Cancer. 2012 Jul 12;12:286. doi: 10.1186/1471-2407-12-286.
The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC).
A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Bim, Noxa, and Puma expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes were analyzed.
Immunohistochemical reactivity for Bim, Noxa, and Puma was detected in the cytoplasm of the tumor cells. Bim expression was associated with several clinicopathological factors, including sex (p < 0.001), smoking habit (p = 0.03), pathological histology (p = 0.001), pathological T stage (p = 0.03), pathological disease stage (p = 0.02), and differentiation of tumor (p < 0.001). Multivariate logistic regression analysis showed a significant correlation between low Bim expression and squamous cell carcinoma (p = 0.04), in addition to a correlation between high Bim expression and well differentiated tumors (p = 0.02). Analysis of cellular biological expression demonstrated a link between low Bim expression and high Ki67. While Noxa expression was also shown to be correlated with both smoking habit (p = 0.02) and the pathological histology (p = 0.03), there was no strong association observed between the expression and the clinical features when they were examined by a multivariate logistic regression analysis. No correlations were noted between Puma expression and any of the variables. Our analyses also indicated that the expression levels of the BH3-only proteins were not pertinent to the survival outcome.
The current analyses demonstrated that Bim expression in the NSCLCs was associated with both squamous cell carcinoma histology and tumor proliferation.
Bcl-2 蛋白家族的 BH3 仅成员被认为在凋亡的控制和凋亡途径的启动中发挥关键作用。在这项研究中,我们评估了非小细胞肺癌 (NSCLC) 中 Bim、Noxa 和 Puma 的表达。
共对 135 例手术切除的 NSCLC 进行了 Bim、Noxa 和 Puma 表达的免疫组织化学评估。确定免疫评分,然后分析其与临床病理变量或生存结果的相关性。
肿瘤细胞的细胞质中检测到 Bim、Noxa 和 Puma 的免疫反应性。Bim 表达与包括性别(p < 0.001)、吸烟习惯(p = 0.03)、病理组织学(p = 0.001)、病理 T 分期(p = 0.03)、病理疾病分期(p = 0.02)和肿瘤分化(p < 0.001)在内的几个临床病理因素相关。多变量逻辑回归分析显示,低 Bim 表达与鳞状细胞癌显著相关(p = 0.04),高 Bim 表达与分化良好的肿瘤相关(p = 0.02)。细胞生物学表达分析表明,低 Bim 表达与高 Ki67 之间存在联系。虽然 Noxa 表达也与吸烟习惯(p = 0.02)和病理组织学(p = 0.03)相关,但当通过多变量逻辑回归分析进行检查时,表达与临床特征之间没有强烈关联。Puma 表达与任何变量之间均无相关性。我们的分析还表明,BH3 仅蛋白的表达水平与生存结果无关。
目前的分析表明,NSCLC 中 Bim 的表达与鳞状细胞癌的组织学和肿瘤增殖有关。