Major pathologic response and RAD51 predict survival in lung cancer patients receiving neoadjuvant chemotherapy
Major pathologic response and RAD51 predict survival in lung cancer patients receiving neoadjuvant chemotherapy
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DOI：
10.1002/cam4.1505
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发表时间：
2018-06-01
期刊：
影响因子：
4
通讯作者：
Swisher, Stephen G.
中科院分区：
文献类型：
--
作者：
Pataer, Apar;Shao, Ruping;Swisher, Stephen G.
在以前的研究中，我们确定了主要病理学反应（MPR），如残留的活肿瘤细胞的百分比预测总生存期（OS）的非小细胞肺癌（NSCLC）患者接受新辅助化疗。在这项研究中，我们评估了两种基因和五种蛋白质生物标志物是否可以预测98例接受新辅助化疗的NSCLC患者的MPR和OS。我们收集了98例接受新辅助化疗的NSCLC患者的福尔马林固定石蜡包埋标本。我们使用焦磷酸测序鉴定KRAS和EGFR基因突变，并使用免疫组织化学检测蛋白标志物VEGFR2、EZH2、ERCC1、RAD51和PKR的表达。我们评估了基因突变状态或蛋白表达是否与MPR或OS相关。我们观察到KRAS突变倾向于与OS相关（P= 0.06），但EGFR突变与OS无关。我们发现，RAD51高表达水平患者的预后比RAD51低表达患者差。我们还观察到RAD51表达与MPR相关。MPR和RAD51表达在单变量和多变量分析中与OS相关（分别为P= 0.04和P= 0.02）。MPR与RAD 51的结合是接受新辅助化疗的非小细胞肺癌患者预后的重要预测因素。我们证明MPR或RAD51表达与接受新辅助化疗的NSCLC患者的OS相关。MPR和RAD51表达的联合评估可提高对患者预后的预测。
In a previous study, we determined that major pathologic response (MPR) as indicated by the percentage of residual viable tumor cells predicted overall survival (OS) in patients with non-small-cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. In this study, we assessed whether two genes and five protein biomarkers could predict MPR and OS in 98 patients with NSCLC receiving neoadjuvant chemotherapy. We collected formalin-fixed, paraffin-embedded specimens of resected NSCLC tumors from 98 patients treated with neoadjuvant chemotherapy. We identified mutations in KRAS and EGFR genes using pyrosequencing and examined the expression of protein markers VEGFR2, EZH2, ERCC1, RAD51, and PKR using immunohistochemistry. We assessed whether gene mutation status or protein expression was associated with MPR or OS. We observed that KRAS mutation tended to be associated with OS (P=.06), but EGFR mutation was not associated with OS. We found that patients with high RAD51 expression levels had a poorer prognosis than did those with low RAD51 expression. We also observed that RAD51 expression was associated with MPR. MPR and RAD51 expression were associated with OS in univariate and multivariate analyses (P=.04 and P=.02, respectively). Combination of MPR with RAD51 is a significant predictor of prognosis in patients with NSCLC who received neoadjuvant chemotherapy. We demonstrated that MPR or RAD51 expression was associated with OS in patients with NSCLC receiving neoadjuvant chemotherapy. Prediction of a patient's prognosis could be improved by combined assessment of MPR and RAD51 expression.