Transcripts related to lung cancer disease in blood samples obtained from diagnostic and pre-diagnostic cohorts

Lung cancer (LC) mortality rates are still increasing globally. As survival is linked to stage, there is a need to identify markers for earlier LC diagnosis and individualized treatment. The circulating transcriptome of LC patients represents a source of potential LC biomarkers. We used genome-wide RNA sequencing to identify LC candidate markers by comparing expression of >60,000 genes in whole blood specimens taken at LC diagnosis from cases (n=128) and controls (n=62). Further, we evaluated expression of these markers in two population-based studies with pre-diagnostic whole blood specimens taken up to eight years prior to LC diagnosis (n=163 cases, 184 matched controls). We identified 14 candidate genes in whole blood associated with LC at diagnosis. High expression of ANXA3, ARG1 and HP was strongly associated with lower survival in late-stage LC cases (adjusted p-values 0.009, 0.03, and 0.007, respectively). We observed strong association of ANXA3 and ARG1 expression with LC also in the pre-diagnostic blood specimens, and especially with late-stage LC within two years of diagnosis (odds ratios 3.47 and 5.00, respectively). Although blood neutrophils were elevated in LC cases both in the diagnostic and pre-diagnostic blood specimens, the observed associations of ANXA3, ARG1 and HP with LC were preserved also after adjusting for elevated blood neutrophils. Our results indicate that in whole blood, increased expression levels of ANXA3, ARG1 and HP are diagnostic and prognostic markers of late-stage LC. mRNA expression profiles from mRNA sequencing of whole blood from lung cancer patients at diagnosis (n=128) and individuals with confirmed negative LC (n=62). >>>Submitter states that raw data are unavailable due to patient privacy concerns<<<