Abstract: Lung cancers are the leading cause of cancer-related deaths worldwide. Studies have shown that non-small cell lung cancer (NSCLC) which constitute majority of lung cancers, are significantly more re-sponsive to early-stage interventions. However, the early stages are often asymptomatic, and current diag-nostic methods are limited in their precision and safety. The cell-free RNAs (cfRNA) circulating in plasma (Liquid biopsies) offer non-invasive detection of spatial and temporal changes occurring in primary tumors since early stages. To address gaps in current cfRNA knowledge base, we conducted a pilot study for com-prehensive analysis of transcriptome-wide changes in plasma cfRNA in NSCLC patients. Total cfRNA was extracted from archived plasma collected from NSCLC patients (N=12; cases), cancer-free former smokers (N=12; control_smokers) and non-smoking healthy volunteers (N=12; control_healthy). Plasma cfRNA ex-pression levels in each sample were quantified by using a tagmentation-based library preparation and se-quencing. The comparisons of cfRNA expression levels between cases and the two control groups revealed a total of 2537 differentially expressed cfRNA enriched in 123 pathways in NSCLC patients. Of these, 222 tran-scripts were previously reported in primary NSCLCs. Our study provides a framework for developing a blood-based assay for early detection of NSCLC and warrants further validation.

The authors have declared no competing interest.

This research was funded by NCI-U24CA11509-01 (SS), FDA-5U01FD005946-06(FJ), and NCI-UH2CA229132 (FJ).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of the University of Maryland Baltimore [UMB IRB protocol ID: HP-00040666] and the Veterans Affairs Maryland Health Care System [protocol ID: VA-00040666].

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All data produced in the present study are available upon reasonable request to the authors