Pathway-Centric Analysis of the TCGA - NSCLC Transcriptome Data Pertaining to Deceased Patients

Abstract

Lung cancer among other cancer types is the most prevalent disease with about 1.9 million new cases observed each year and ranks the fifth most common cause of death according to the World Health Organization. Of the two main subtypes of lung cancer, non-small cell lung carcinoma (NSCLC) accounts for the majority of all cases. The two major subtypes of NSCLC, lung squamous cell carcinoma and lung adenocarcinoma are extensively sampled as part of The Cancer Genome Atlas (TCGA) project. In this study, we took a pathway centric focus on the analysis of RNA-Seq data belonging to dead NSCLC patients involved in TCGA. We applied statistical tests comparing subgroups of patients based on varying clinical traits such as tumor pathologic staging and the total number of days passed from diagnosis till death for the subjected patients. We also compared the transcriptome of smokers and nonsmokers to gain insights about the effect of tobacco smoking history on the gene expression patterns of deceased NSCLC patients. Neuroactive ligand-receptor interaction pathway was overrepresented in patients who died at pathologic T2 stage as well as in those lung cancer patients who survived less than a year. Down-regulation of the signaling pathways such as retrograde endocannabinoid, Hippo, AGE-RAGE in diabetic complications, Wnt, and oxytocin was also striking in patients who survived shorter. We show concordant results with previous findings about the down-regulation of nitric oxide synthase in smokers. This study may encourage more focused analyses of the TCGA data with a potential to cast new perspectives onto lung cancer research.