Comprehensive Evaluation of Nuclear Factor-κΒ Expression Patterns in Non-Small Cell Lung Cancer.
Comprehensive Evaluation of Nuclear Factor-κΒ Expression Patterns in Non-Small Cell Lung Cancer.
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DOI：
10.1371/journal.pone.0132527
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Stathopoulos GT
中科院分区：
文献类型：
--
作者：
Giopanou I;Lilis I;Papaleonidopoulos V;Marazioti A;Spella M;Vreka M;Papadaki H;Stathopoulos GT
核因子（NF）-κB信号传导是小鼠肺腺癌发生所必需的，其亚基RelA和RelB在人非小细胞肺癌（NSCLC）中高度表达。为了全面检测NF-κB在非小细胞肺癌中的表达，我们分析了77例有充分记录的患者（36例腺癌，40例鳞状细胞癌和3例大细胞癌）原发肿瘤样本的连续切片中RelA、RelB、P50和P52/P100的免疫反应性。根据增殖细胞核抗原免疫反应性区分肿瘤和瘤内间质区域，并评估瘤内间质区域的炎症浸润。NF-κB免疫反应性通过强度、范围和核定位进行定量，并与肿瘤细胞增殖、炎症浸润和临床病理数据进行交叉检查。我们发现不同NF-κB亚基的表达并不一致，这与我们的积分方法不符。总体而言，RelA、RelB和P50的表达水平高于P52/P100。RelA和P50主要表达于肿瘤间质，而RelB主要表达于肿瘤细胞。重要的是，肿瘤区域RelA表达与炎症浸润的强度相关，而RelB表达在增殖的肿瘤细胞中被鉴定。使用多元逻辑回归，我们确定肿瘤RelB表达是淋巴结转移的独立预测因子，肿瘤P50是TNM 6 IIB或更高分期的独立预测因子，而肿瘤RelA是炎症浸润的独立预测因子。我们的结论是，NF-κB在癌症中的表达的病理学研究应该包括多个途径的组成部分。利用这种方法，我们确定了不同的NF-κB亚基与NSCLC的临床和病理特征之间有趣的关联。
Nuclear factor (NF)-κB signalling is required for lung adenocarcinoma development in mice, and both of its subunits RelA and RelB were independently reported to be highly expressed in human non-small cell lung cancer (NSCLC). To comprehensively examine NF-κB expression in NSCLC, we analyzed serial sections of primary tumor samples from 77 well-documented patients (36 adenocarcinomas, 40 squamous cell carcinomas and 3 large cell carcinomas) for immunoreactivity of RelA, RelB, P50, and P52/P100. Tumor and intratumoral stroma areas were discriminated based on proliferating cell nuclear antigen immunoreactivity and inflammatory infiltration was assessed in intratumoral stroma areas. NF-κB immunoreactivity was quantified by intensity, extent, and nuclear localization and was cross-examined with tumor cell proliferation, inflammatory infiltration, and clinical-pathologic data. We found that the expression of the different NF-κB subunits was not concordant, warranting our integral approach. Overall, RelA, RelB, and P50 were expressed at higher levels compared with P52/P100. However, RelA and P50 were predominantly expressed in intratumoral stroma, but RelB in tumor cells. Importantly, tumor area RelA expression was correlated with the intensity of inflammatory infiltration, whereas RelB expression was identified in proliferating tumor cells. Using multiple logistic regression, we identified that tumor RelB expression was an independent predictor of lymph node metastasis, and tumor P50 was an independent predictor of TNM6 stage IIB or higher, whereas tumor RelA was an independent predictor of inflammatory infiltration. We conclude that pathologic studies of NF-κB expression in cancer should include multiple pathway components. Utilizing such an approach, we identified intriguing associations between distinct NF-κB subunits and clinical and pathologic features of NSCLC.
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影响因子：
2.8
作者：
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通讯作者：
Saad, F
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