Differential expression of circulating biomarkers of tumor phenotype and outcomes in previously treated non-small cell lung cancer patients receiving erlotinib vs. cytotoxic chemotherapy.

Autor:	Fidler MJ; Section of Medical Oncology, Rush University Medical Center, Chicago, IL 60612, USA., Frankenberger C; Pathology, Rush University Medical Center, Chicago, IL 60612, USA., Seto R; Section of Medical Oncology, Rush University Medical Center, Chicago, IL 60612, USA., Lobato GC; Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA., Fhied CL; Pathology, Rush University Medical Center, Chicago, IL 60612, USA., Sayidine S; Pathology, Rush University Medical Center, Chicago, IL 60612, USA., Basu S; Preventative Medicine, Rush University Medical Center, Chicago, IL 60612, USA., Pool M; Pathology, Rush University Medical Center, Chicago, IL 60612, USA., Karmali R; Hematology, Oncology and Cell Therapy at Rush University Medical Center, Chicago, IL 60612, USA.; Present address: Division of Hematology and Oncology, Northwestern University, Chicago, IL 60612, USA., Batus M; Section of Medical Oncology, Rush University Medical Center, Chicago, IL 60612, USA., Lie WR; EMD Millipore Corporation, St. Charles, MO 63304, USA., Hayes D; EMD Millipore Corporation, St. Charles, MO 63304, USA., Mistry J; EMD Millipore Corporation, St. Charles, MO 63304, USA., Bonomi P; Section of Medical Oncology, Rush University Medical Center, Chicago, IL 60612, USA., Borgia JA; Pathology, Rush University Medical Center, Chicago, IL 60612, USA.; Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Apr 28; Vol. 8 (35), pp. 58108-58121. Date of Electronic Publication: 2017 Apr 28 (Print Publication: 2017).
DOI:	10.18632/oncotarget.17510
Abstrakt:	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-2Rα, FGF-2) processes and a pro-angiogenic (e.g. TGF-α, 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. Competing Interests: CONFLICTS OF INTEREST Several of the authors (WRL, DH, and JM) were employees of EMD Millipore at the time of study performance; this fact in no way influenced any of the experimental design or interpretation of results presented in this article. Otherwise, the remaining authors have no competing interests to declare.
Databáze:	MEDLINE
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