Affiliation:
1. Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P. R. China
2. Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer Chinese Academy of Medical Sciences Beijing P. R. China
3. Department of Thoracic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong P. R. China
4. Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P. R. China
Abstract
AbstractIntroductionWith the advancements in early diagnosis, more and more patients with multiple primary lung cancer (MPLC) have been identified. However, the progression of MPLC involves complex changes in cell composition and metabolic function, which remains largely controversial.ObjectiveOur study aims to comprehensively reveal the cellular characteristics and inter‐cellular connections of MPLC.MethodsWe performed scRNA‐seq from 23 samples of six MPLC patients, combined with bulk whole‐exome sequencing. We performed trajectory analysis to investigate the transition of different cell types during the development of MPLC.ResultsA total of 1 67 397 cells were sequenced derived from tumour and adjacent tissues of MPLC patients, and tumour, normal, immune and stromal cells were identified. Two states of epithelial cells were identified, which were associated with immune response and cell death, respectively. Furthermore, both CD8+ naïve and memory T cells participated in the differentiation of CD8+ T cells. The terminal states of CD8+ T cells were exhausted T cells and cytotoxic T cells, which positively regulated cell death and were implicated in the regulation of cytokine production, respectively. Two main subpopulations of B cells with distinct functions were identified, which participate in the regulation of the immune response and antigen presentation, respectively. In addition, we found a specific type of endothelial cells that were abundant in tumour samples, with an increasing trend from normal to tumour samples.ConclusionsOur study showed the comprehensive landscape of different cells of MPLC, which might reveal the key cellular mechanisms and, therefore, may provide new insights into the early diagnosis and treatment of MPLC.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Subject
Molecular Medicine,Medicine (miscellaneous)