Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma

Many studies support a stepwise continuum of morphologic changes between atypical adenomatous hyperplasia (AAH) and lung adenocarcinoma (ADC). Here we characterized gene expression patterns and the association of differentially expressed genes and immune tumor microenvironment behaviors in AAH to ADC during ADC development. Tumor tissues from nine patients with ADC and synchronous multiple ground glass nodules/lesions (GGN/Ls) were analyzed using RNA sequencing. Using clustering, we identified genes differentially and sequentially expressed in AAH and ADC compared to normal tissues. Functional enrichment analysis using gene ontology terms was performed, and the fraction of immune cell types was estimated. We identified up-regulated genes (ACSL5 and SERINC2) with a stepwise change of expression from AAH to ADC and validated those expressions by quantitative PCR and immunohistochemistry. The immune cell profiles revealed increased B cell activities and decreased natural killer cell activities in AAH and ADC. A stepwise change of differential expression during ADC development revealed potential effects on immune function in synchronous precursors and in tumor lesions in patients with lung cancer.

Automated summary

The study identified gene expression patterns and immune tumor microenvironment behaviors in the continuum from atypical adenomatous hyperplasia (AAH) to lung adenocarcinoma (ADC). Up-regulated genes with stepwise change of expression from AAH to ADC were found, as well as differences in immune cell profiles between AAH and ADC. The differential expression during ADC development was found to potentially affect immune function in synchronous precursors and tumor lesions in patients with lung cancer.