Michael F Sharpnack1, Nilini Ranbaduge2, Arunima Srivastava3, Ferdinando Cerciello4, Simona G Codreanu5, Daniel C Liebler6, Celine Mascaux7, Wayne O Miles8, Robert Morris8, Jason E McDermott9, James L Sharpnack10, Joseph Amann11, Christopher A Maher12, Raghu Machiraju3, Vicki H Wysocki2, Ramaswami Govindan12, Parag Mallick13, Kevin R Coombes1, Kun Huang1, David P Carbone14. 1. Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio. 2. Department of Chemistry, The Ohio State University, Columbus, Ohio. 3. Department of Computer Science and Engineering, The Ohio State University, Columbus, Ohio. 4. Department of Oncology, University Hospital Zurich, Zürich, Switzerland. 5. Department of Chemistry, Vanderbilt University, Nashville, Tennessee. 6. Department of Biochemistry, Vanderbilt University, Nashville, Tennessee. 7. Department of Multidisciplinary Oncology and Therapeutic Innovations, Assistance Publique des Hôpitaux de Marseille, France; Aix-Marseille University, Marseille, France. 8. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts. 9. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA. 10. Department of Statistics, University of California, Davis, California. 11. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. 12. Department of Medicine, Washington University in St. Louis, St. Louis, Missouri. 13. Department of Radiology, Stanford University, Palo Alto, California. 14. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Electronic address: david.carbone@osumc.edu.
Abstract
INTRODUCTION: Despite apparently complete surgical resection, approximately half of resected early-stage lung cancer patients relapse and die of their disease. Adjuvant chemotherapy reduces this risk by only 5% to 8%. Thus, there is a need for better identifying who benefits from adjuvant therapy, the drivers of relapse, and novel targets in this setting. METHODS: RNA sequencing and liquid chromatography/liquid chromatography-mass spectrometry proteomics data were generated from 51 surgically resected non-small cell lung tumors with known recurrence status. RESULTS: We present a rationale and framework for the incorporation of high-content RNA and protein measurements into integrative biomarkers and show the potential of this approach for predicting risk of recurrence in a group of lung adenocarcinomas. In addition, we characterize the relationship between mRNA and protein measurements in lung adenocarcinoma and show that it is outcome specific. CONCLUSIONS: Our results suggest that mRNA and protein data possess independent biological and clinical importance, which can be leveraged to create higher-powered expression biomarkers.
INTRODUCTION: Despite apparently complete surgical resection, approximately half of resected early-stage lung cancerpatients relapse and die of their disease. Adjuvant chemotherapy reduces this risk by only 5% to 8%. Thus, there is a need for better identifying who benefits from adjuvant therapy, the drivers of relapse, and novel targets in this setting. METHODS: RNA sequencing and liquid chromatography/liquid chromatography-mass spectrometry proteomics data were generated from 51 surgically resected non-small cell lung tumors with known recurrence status. RESULTS: We present a rationale and framework for the incorporation of high-content RNA and protein measurements into integrative biomarkers and show the potential of this approach for predicting risk of recurrence in a group of lung adenocarcinomas. In addition, we characterize the relationship between mRNA and protein measurements in lung adenocarcinoma and show that it is outcome specific. CONCLUSIONS: Our results suggest that mRNA and protein data possess independent biological and clinical importance, which can be leveraged to create higher-powered expression biomarkers.
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