Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients.

Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients.
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p53/p21 表达和吸烟与非小细胞肺癌患者肿瘤进展和不良预后的关系。

DOI:
10.3892/or.2014.3538
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发表时间:
2014-12
期刊:
影响因子:
4.2
通讯作者:
Lu, Bin
Lu, Bin
中科院分区:
医学3区
文献类型:
--
作者:
Wu, Xiaoyi;Wang, Lu;Liu, Yongzhang;Lu, Bin

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非小细胞肺癌 (NSCLC) 约占所有肺癌病例的 80-85%。吸烟是第一大危险因素,五分之四以上的肺癌病例是由吸烟引起的。细胞周期调节相关肿瘤抑制因子(包括 p53 和 p21)对 NSCLC 的预后影响仍存在争议。在本研究中,我们使用免疫印迹法检测了 NSCLC 患者肿瘤和邻近非癌组织中 p53 和 p21 的表达。此外,使用包含 150 个样本的组织微阵列 (TMA) 通过免疫组织化学染色 (IHC) 检查 p53 和 p21 的表达。评估了 p53/p21 与各种临床病理特征之间的关联。采用Kaplan-Meier总生存分析p53/p21表达与NSCLC患者预后的关系,以及吸烟与p53/p21表达及预后的关系。免疫印迹结果显示,肿瘤组织中p53和p21的表达显着高于相匹配的癌旁非癌组织(分别P<0.001和P<0.05)。 IHC结果显示,50.67%的病例p21高表达;然而,p53高表达的患者比例为31.3%。采用单变量和Cox回归模型评估p53和p21表达与预后相关的因素。多因素分析显示p53表达是NSCLC的独立预后因素(P=0.005),而p21不能作为独立的预后因素(P=0.123)。此外,吸烟史与肺癌风险密切相关(P=0.041),但不能作为独立的评估因素(P=0.740)。在这项研究中,我们进一步证明了 p53/p21 表达与吸烟的关联。我们的结果表明吸烟和 p53 或 p21 过度表达与不良预后相关。 p53/p21表达和吸烟史的结合可能是NSCLC患者肿瘤进展和预后的有用生物标志物。
Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. Cigarette smoking is the number one risk factor which is attributed to more than four out of five cases of lung cancers. The prognostic impact of cell cycle regulation-associated tumor suppressors including p53 and p21 for NSCLC is still controversial. In the present study, we examined p53 and p21 expression using immunoblotting in tumor and adjacent non-cancerous tissues from NSCLC patients. Moreover, tissue microarrays (TMAs) including 150 specimens was used to examine p53 and p21 expression by immunohistochemical staining (IHC). The association between p53/p21 and various clinicopathological characteristics was evaluated. Kaplan-Meier overall survival was used to analyze the association between p53/p21 expression and prognosis of NSCLC patients, as well as the association of cigarette smoking with p53/p21 expression and prognosis. The results of the immunoblotting showed that expression of p53 and p21 in tumor tissues was significantly higher than that in the matched adjacent non-cancerous tissues (P<0.001 and P<0.05, respectively). The IHC results showed that 50.67% of the cases had high expression of p21; however, the percentage of patients having high expression of p53 was 31.3%. Univariate and Cox regression models were used to evaluate the factors related to prognosis with p53 and p21 expression. Multivariate analysis indicated that p53 expression was an independent prognostic factor for NSCLC (P=0.005), while p21 could not serve as an independent prognostic factor (P=0.123). In addition, smoking history was closely related to lung cancer risk (P=0.041), but could not be an independent assessment factor (P=0.740). In this study, we further demonstrated the association of p53/p21 expression and cigarette smoking. Our results suggest that cigarette smoking and overexpression of p53 or p21 are associated with poor prognosis. The combination of p53/p21 expression and smoking history may be a useful biomarker for tumor progression and prognosis of NSCLC patients.
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