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.
Highlights
Lung cancer is traditionally classified as non– small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) [1]
We examined the impact of gene expression levels in primary tumors on the progression status in non–small-cell lung cancer (NSCLC) patients following surgical treatment
We went on to explore the prognostic power of genes that were differentially expressed in lung squamous cell carcinomas (LUSC) versus lung adenocarcinomas (LUAD)
Summary
Lung cancer is traditionally classified as non– small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) [1]. The two cancer types differ in histopathological traits, genetic changes, prognosis and response to therapy [1]. While the usefulness of distinguishing NSCLC from SCLC is clear, far less clear is the reason for jointly categorizing distinct NSCLC subtypes. NSCLC is the most common type of lung cancer, with a poor response to chemotherapy and a low survival rate. This unfavorable treatment response stems from both late diagnosis and from complex, incompletely understood biology. The two main NSCLC histopathological subtypes are lung adenocarcinomas (LUAD) and lung squamous cell carcinomas (LUSC). To define the contribution of major cellular pathways to the biogenesis of LUAD versus LUSC, we profiled their transcriptomic signatures, identified the corresponding control networks and defined key prognostic determinants of biological outcome
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