Integrated analysis of genomic and microenvironment characteristics associated with pathology and radiology features in patients with early multifocal lung nodules.

Abstract

e20519 Background: Pulmonary nodules are distinct clinical entities, and patients with different pulmonary nodules have different rates of progression to lung cancer. However, the genomic and microenvironment features of different pulmonary nodules are still unclear. Methods: 2 to 3 pulmonary nodules and matched paracancerous tissue were collected from 10 patients. Whole-exome sequencing and RNA sequencing were performed for each sample. The genomic and microenvironment characteristics were analyzed based on pathology (AIS/MIA/IA) and radiology (pGGO/mGGO/solid) features. Results: At genomic level, tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were significantly increased with the development of the nodules. The most frequent mutation genes EGRF and KRAS were mutated exclusively. TMB and TNB in nodules with EGFR or KRAS mutation were significantly increased compared with nodules without these mutations and paracancerous. Transcriptome analysis revealed that energy metabolism signal pathways was upregulated in early stages (pGGO/AIS), while immune-related signal pathways were upregulated in latter stages (mGGO/IA). And in EGFR mutated nodules, cytokine-cytokine-receptor signal pathways were upregulated. Furter, tumor microenvironment was analyzed, and it was found that DCs, B cells and CD4+ T cells were significantly increased while endothelial and myocytes were significantly decreased with the development of the nodules. In addition, DCs were found to be significantly increased in EGFR mutated nodules when compared with KRAS mutated nodules. Conclusions: In this study, some genomic and tumor microenvironment biomarkers in different developmental stages of lung nodules were found, which may provide basis for the development of accurate diagnosis and classification of pulmonary nodules.