Dissecting transcriptional heterogeneity in multiple primary lung cancer by single cell RNA sequencing.

Abstract

e20516 Background: The progression of multiple primary lung cancer has been involved in complex cell changes in composition and metabolic function. However, the role of immune related cells proliferation and epithelial cells differentiation during the synchronous multiple primary lung cancer development is still understudied. Methods: In this study, we performed scRNA sequencing of 167,397 cells from six patients with multiple primary lung cancer, combined with bulk RNAseq and whole exome sequencing. Results: We firstly revealed that both naïve and memory T cells participated in the differentiation of CD8+ T cells. One end state of CD8+ T cells is exhausted T cells and they response to stimulus and positive regulated the cell death. The Other end state is cytotoxic T cells which mainly implicated in regulation of cytokine production included positive regulation of myeloid leukocyte cytokine production involved in immune response, immune effector process, macrophage cytokine production and positive regulation of cytokine production involved in immune response. Multiple functional Treg cells and naïve T cells contributed to the CD4+ T cells origin. In addition, B cells with two main kinds of function also plays an important role in immune response. One is that the regulation and activation of innate immune response have been highly activated. The other were enriched in pathways that antigen binding, processing and presentation including MHC class II Antigen Presentation. We also revealed the cellular metabolic functions during the tumor invasion. The positive regulation of blood vessel diameter has been observed in endothelial cells, while angiogenesis has not been found in early glandular neoplasia of the lung. The development of epithelial cells mainly consists of two function states. One is that some cells response to the stress from immune, and the other is that some will die programmatically and begin to cell circle due to selective pressure with the development of tumor in multiple primary lung cancer. Conclusions: Our study showed a complete landscape of different dynamic cellular changes which might pinpoint the key cellular mechanisms of synchronous multiple primary lung cancer and therefore provided new clues for pathogenesis of tumors.