Mechanisms of Progression and Heterogeneity in Multiple Nodules of Lung Adenocarcinoma

Abstract Lung cancer remains the leading cause of cancer‐related death worldwide. Lung adenocarcinoma (LUAD) is thought to be caused by precursor lesions of atypical adenoma‐like hyperplasia and may have extensive in situ growth before infiltration. To explore the relevant factors in heterogeneity and evolution of lung adenocarcinoma subtypes, the authors perform single‐cell RNA sequencing (scRNA‐seq) on tumor and normal tissue from five multiple nodules’ LUAD patients and conduct a thorough gene expression profiling of cancer cells and cells in their microenvironment at single‐cell level. This study gives a deep understanding of heterogeneity and evolution in early glandular neoplasia of the lung. This dataset leads to discovery of the changes in the immune microenvironment during the development of LUAD, and the development process from adenocarcinoma in situ (AIS) to invasive adenocarcinoma (IAC). This work sheds light on the direction of early tumor development and whether they are homologous.