Distinct lung cancer subtypes associate to distinct drivers of tumor progression

// Valeria Relli 1 , Marco Trerotola 1, 2 , Emanuela Guerra 1, 2 and Saverio Alberti 1, 3 1 Unit of Cancer Pathology, CeSI-MeT, University “G. d’Annunzio”, Chieti, Italy 2 Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio”, Chieti, Italy 3 Department of Biomedical Sciences, Dentistry, Morphological and Functional Imaging, University of Messina, Messina, Italy Correspondence to: Saverio Alberti, email: salberti@unime.it Keywords: non-small cell lung cancer; lung adenocarcinomas; lung squamous cell carcinomas; prognostic determinants; survival curves Received: August 31, 2018      Accepted: September 26, 2018      Published: October 30, 2018 ABSTRACT The main non–small-cell lung cancer (NSCLC) histopathological subtypes are lung adenocarcinomas (LUAD) and lung squamous cell carcinomas (LUSC). To identify candidate progression determinants of NSCLC subtypes, we explored the transcriptomic signatures of LUAD versus LUSC. We then investigated the prognostic impact of the identified tumor-associated determinants. This was done utilizing DNA microarray data from 2,437 NSCLC patients. An independent analysis of a case series of 994 NSCLC was conducted by next-generation sequencing, together with gene expression profiling from GEO ( https://www.ncbi.nlm.nih.gov/geo/ ). This work led us to identify 69 distinct tumor prognostic determinants, which impact on LUAD or LUSC clinical outcome. These included key drivers of tumor growth and cell cycle, transcription factors and metabolic determinants. Such disease determinants appeared vastly different in LUAD versus LUSC, and often had opposite impact on clinical outcome. These findings indicate that distinct tumor progression pathways are at work in the two NSCLC subtypes. Notably, most prognostic determinants would go inappropriately assessed or even undetected when globally investigating unselected NSCLC. Hence, differential consideration for NSCLC subtypes should be taken into account in current clinical evaluation procedures for lung cancer.