Non-Small Cell Lung Cancer, Peripheral Immunity, Extending the Tumor Macroenvironment

We recently established that gene expression in PAXgene stabilized blood RNA distinguishes benign (BN) from malignant (MN) pulmonary nodules in high risk candidates with an AUC of 0.84. We now expand our studies to include incidental nodules identified in routine clinical settings using data from 603 patients analyzed on Illumina microarrays. We identify 300 gene probes achieving an AUC of 0.84 for Indeterminate Pulmonary Nodules (IPN) from 6-25 mm and 0.824 for IPN from 8-20 mm, outperforming 3 prominent clinical models that achieve AUCs of 0.60-0.689. We address the basis for these differences by in silico flow cytometry using CIBERSORT and identify significant differences between MN and BN patients including proportions of T-cells, M0 macrophages, NK cells, B cells and exhausted CD8 T-cells. We identify major increases in expression of genes promoting cell death and strong decreases in functions promoting transcription, lymphogenesis and cell viability. A preferential use of oxidative phosphorylation and a signature of mitochondrial dysfunction are also associated with the presence of a MN. Whole blood gene expression from patients with malignant (MN), benign (BN) nodules and patients with no nodules (NN)