期刊
ONCOTARGET
卷 8, 期 35, 页码 58108-58121出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17510
关键词
biomarker; non-small cell lung cancer (NSCLC); Luminex; erlotinib; epithelial-to-mesenchymal transition (EMT)
资金
- American Cancer Society, Illinois Chapter
- Respiratory Health Association of Metropolitan Chicago
Background: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. Methods: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n= 79). Known EGFR mutation positive cases were excluded from analysis. Associations of biomarkers with outcome parameters and their differential interaction with treatment for survival outcomes were assessed using multivariate Cox PH analyses. Results: Our EMT-based transcriptomic analysis revealed a range of biological processes associated with angiogenesis, apoptosis, cachexia, inflammation, and metabolism emerging as those most highly associated with patient outcome. These processes were evaluated via surrogate serum biomarkers. A treatment-biomarker interaction analysis revealed that higher pretreatment levels of c-Met signaling biomarkers (i.e. HGF levels), pro-inflammatory/pro-cachexia (e.g. IL-8, sIL-2R alpha, FGF2) processes and a pro-angiogenic (e.g. TGF-alpha, IL-8, VEGF) milieu were associated with inferior survival (HR= 0.35, 0.29, 0.58, 0.50, 0.61, 0.45, respectively; all p< 0.05) for patients receiving chemotherapy, relative to erlotinib. In contrast, high levels of decoy receptor for IL-1, sIL-1RII, and a high tissue vimentin/E-cadherin ratio were associated with a poor OS (HR= 3.78; p= 0.00055) in the erlotinib cohort. Conclusions: Contemporary precision medicine initiatives that pair patient tumor characteristics with the optimal therapy type may maximize the use of agents targeting EGFR in the treatment of NSCLC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据