Confounding effects of benign lung diseases on non-small cell lung cancer serum biomarker discovery

Abstract

Introduction: Lung cancer is the leading cause of cancer-related death worldwide. The discovery of new biomarkers could aid early diagnosis and monitoring of recurrence following tumor resection. Methods: We have prospectively collected serum from 97 lung cancer patients undergoing surgery with curative intent and compared their serum proteomes with those of 100 noncancer controls (59 disease-free and 41 with a range of nonmalignant lung conditions). We initially analyzed serum from 67 lung cancer patients and 73 noncancer control subjects by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry using immobilized metal affinity capture ProteinChip arrays and subsequently validated our findings with an independent analysis of 30 lung cancer patients and 27 noncancer subjects. Results: The data from both experiments show many significant differences between the serum proteomes of lung cancer patients and nondiseased control subjects, and a number of these polypeptides have been identified. However, the profiles of patients with benign lung diseases resembled those of lung cancer patients such that very few significant differences were found when these cohorts were compared. Conclusions: This report provides clear evidence of the need to account for the confounding effects of benign diseases when designing lung cancer serum biomarker discovery projects. © 2009 Humana Press.