Single-patient single-cell RNA sequencing reveals neuroendocrine predominance and immunosuppression in small-cell lung cancer.

[BACKGROUND] Small cell lung cancer (SCLC) is a subtype of lung cancer that is aggressive, progresses rapidly, and is prone to recurrence. The biological composition of SCLC is still under investigation. This study aims to characterize the intratumoral heterogeneity and immunosuppressive tumor microenvironment of SCLC using single-cell RNA sequencing (scRNA-seq), and to identify and validate the key genes and as potential therapeutic targets.

[METHODS] To comprehend the heterogeneity of SCLC and the tumor microenvironment, we used scRNA-seq to analyze the primary tumor and adjacent noncancerous tissue from a patient. The findings were tested with cell experiments.

[RESULTS] We observed that SCLC was mainly composed of neuroendocrine epithelial cells and displayed the immune-related cell failure state. The corresponding antitumor immune pathway activities were also downregulated, and the tumor microenvironment eventually showed immunosuppression. BEX1 and MAP1b were upregulated in most cell subtypes, which are verified by immunohistochemistry. In addition, downregulation of BEX1 in NCI-H209 and MAP1b in NCI-H82 significantly inhibited cell proliferation and migration, while increasing apoptosis. Based on preliminary data, BEX1 and MAP1b have been identified as promising candidates for the early diagnosis and therapy of SCLC; however, their clinical utility requires confirmation in subsequent studies. To investigate the heterogeneity and interaction among different cell types, we also constructed an intercellular communication network.

[CONCLUSIONS] Our knowledge of the basic traits of SCLC is improved by this highly accurate single-cell study, which also offers fresh suggestions for potential future therapies.