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: | Richard Seto, Casey Frankenberger, Marta Batus, Jehangir Mistry, Selina Sayidine, David Hayes, Philip Bonomi, Cristina Fhied, Mary J. Fidler, Gabriela C. Lobato, Sanjib Basu, Jeffrey A. Borgia, Wen Rong Lie, Mark Pool, Reem Karmali |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology erlotinib medicine.medical_specialty medicine.medical_treatment non-small cell lung cancer (NSCLC) Cachexia 03 medical and health sciences 0302 clinical medicine Internal medicine Luminex medicine Lung cancer Chemotherapy Hematology business.industry medicine.disease Precision medicine 030104 developmental biology 030220 oncology & carcinogenesis Immunology biomarker Biomarker (medicine) Erlotinib business epithelial-to-mesenchymal transition (EMT) Research Paper medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.17510 |
| Popis: | // Mary Jo Fidler 1 , Casey Frankenberger 2 , Richard Seto 1 , Gabriela C. Lobato 3 , Cristina L. Fhied 2 , Selina Sayidine 2 , Sanjib Basu 4 , Mark Pool 2 , Reem Karmali 5, 6 , Marta Batus 1 , Wen-Rong Lie 7 , David Hayes 7 , Jehangir Mistry 7 , Philip Bonomi 1 and Jeffrey A. Borgia 2, 3 1 Section of Medical Oncology, Rush University Medical Center, Chicago, IL 60612, USA 2 Pathology, Rush University Medical Center, Chicago, IL 60612, USA 3 Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA 4 Preventative Medicine, Rush University Medical Center, Chicago, IL 60612, USA 5 Hematology, Oncology and Cell Therapy at Rush University Medical Center, Chicago, IL 60612, USA 6 Present address: Division of Hematology and Oncology, Northwestern University, Chicago, IL 60612, USA 7 EMD Millipore Corporation, St. Charles, MO 63304, USA Correspondence to: Jeffrey A. Borgia, email: Jeffrey_Borgia@Rush.edu Keywords: biomarker, non-small cell lung cancer (NSCLC), Luminex, erlotinib, epithelial-to-mesenchymal transition (EMT) Received: October 11, 2016 Accepted: February 06, 2017 Published: April 28, 2017 ABSTRACT 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|