RAD50 Expression Is Associated with Poor Clinical Outcomes after Radiotherapy for Resected Non-small Cell Lung Cancer
RAD50 Expression Is Associated with Poor Clinical Outcomes after Radiotherapy for Resected Non-small Cell Lung Cancer
复制标题
DOI：
10.1158/1078-0432.ccr-17-1455
复制
发表时间：
2018-01-15
影响因子：
11.5
通讯作者：
Lin, Steven H.
中科院分区：
文献类型：
--
作者：
Wang, Yifan;Gudikote, Jayanthi;Lin, Steven H.
目的：虽然术后放疗通常用于维持局部晚期非小细胞肺癌（NSCLC）手术切除和化疗后的局部控制，但局部区域失败和远处转移仍然存在问题。治疗耐药的机制仍然知之甚少。实验设计：我们使用反相蛋白阵列（RPPA）的配置文件的基线表达的170个总的和磷酸化的蛋白质在70个NSCLC细胞系分类的途径，可能有助于辐射抗性。在组织微阵列（TMA）中进一步分析了127例在接受术后放疗前接受手术的NSCLC患者的标本中RPPA鉴定的重要标志物。采用考克斯回归分析和对数秩检验确定潜在的预测因素。然后，我们验证的生物学功能的标记物在NSCLC细胞株在vitro.Results：的170蛋白质或磷蛋白的轮廓，一个子集的12个蛋白质被发现与辐射反应参数。在RPPA分析中显示表达差异最大的12种蛋白质的TMA分析表明，RAD50与NSCLC患者的远端无复发生存期、局部无复发生存期和无病生存期具有最强的相关性。我们证实，敲低RAD50敏感的NSCLC细胞辐射和RAD50的上调增加在体外experiments.Conclusions：上调RAD50可能是一个预测的放射抵抗的肺癌患者接受放射治疗。(C)2017年AACR。
Purpose: Although postoperative radiotherapy is often used to maintain local control after surgical resection and chemotherapy for locally advanced non-small cell lung cancer (NSCLC), both locoregional failure and distant metastasis remain problematic. The mechanisms of therapeutic resistance remain poorly understood.Experimental Design: We used reverse-phase protein arrays (RPPA) to profile the baseline expression of 170 total and phosphorylated proteins in 70 NSCLC cell lines to categorize pathways that may contribute to radiation resistance. Significant markers identified by RPPA were further analyzed in tissue microarrays (TMA) of specimens from 127 patients with NSCLC who had received surgery before receiving postoperative radiotherapy. Cox regression analysis and log-rank tests were used to identify potential predictive factors. We then validated the biological function of the markers in NSCLC cell lines in vitro.Results: Of the 170 proteins or phospho-proteins profiled, a subset of 12 proteins was found to correlate with radiation response parameters. TMA analysis of the 12 proteins showing the greatest differences in expression in the RPPA analysis demonstrated that RAD50 had the strongest correlation with distant relapse-free survival, locoregional relapse-free survival, and disease-free survival in patients with NSCLC. We confirmed that knockdown of RAD50 sensitized NSCLC cells to radiation and that upregulation of RAD50 increased radioresistance in in vitro experiments.Conclusions: Upregulated RAD50 may be a predictor of radioresistance in patients with lung cancer who received radiotherapy. (C) 2017 AACR.