Non‐invasive lung cancer diagnosis by detection of GATA 6 and NKX 2‐1 isoforms in exhaled breath condensate

Abstract

Lung cancer ( LC ) is the leading cause of cancer‐related deaths worldwide. Early LC diagnosis is crucial to reduce the high case fatality rate of this disease. In this case–control study, we developed an accurate LC diagnosis test using retrospectively collected formalin‐fixed paraffin‐embedded ( FFPE ) human lung tissues and prospectively collected exhaled breath condensates ( EBC s). Following international guidelines for diagnostic methods with clinical application, reproducible standard operating procedures ( SOP ) were established for every step comprising our LC diagnosis method. We analyzed the expression of distinct mRNA s expressed from GATA 6 and NKX 2‐1 , key regulators of lung development. The Em/Ad expression ratios of GATA 6 and NKX 2‐1 detected in EBC s were combined using linear kernel support vector machines ( SVM ) into the LC score, which can be used for LC detection. LC score‐based diagnosis achieved a high performance in an independent validation cohort. We propose our method as a non‐invasive, accurate, and low‐price option to complement the success of computed tomography imaging ( CT ) and chest X‐ray ( CXR ) for LC diagnosis. image Early diagnosis is critical to improving lung cancer ( LC ) patient prognosis. An accurate, non‐invasive LC diagnostic test was developed based on expression analysis of embryonic vs. adult GATA 6 and NKX 2‐1 gene isoforms in exhaled breath condensates. Embryonic and adult isoforms of GATA 6 and NKX 2‐1 are differentially expressed during mouse lung development and in lung cancer. RNA purified from exhaled breath condensates ( EBC ) can be used for qRT – PCR ‐based expression analysis, despite the relatively high fragmentation of the isolated RNA . Embryonic and adult isoforms of GATA 6 and NKX 2‐1 detected in EBC can be combined into the LC score for LC diagnosis at stages I and II .