Single-Cell Transcriptome Sequencing and Analysis Provide a New Approach for the Treatment of Small Cell Neuroendocrine Carcinoma of the Cervix.

Abstract

Introduction: Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare gynecologic malignant tumor, which has lack of systematic research. In order to investigate its molecular characteristics, origin, and pathogenesis, single-cell transcriptome sequencing (scRNA-Seq) of SCNECC was performed for the first time, the cellular and molecular landscape was revealed, and the key genes for clinical prognosis were screened.

Methods: This article initially performed the scRNA-Seq on a tumor tissue sample from an SCNECC patient, combined with scRNA-Seq data from a healthy cervical tissue sample downloaded from a public database; the single-cell transcriptome landscape was constructed. Then, we investigated the cell types, intratumoral heterogeneity, characteristics of tumor microenvironment, and potential predictive markers of SCNECC.

Results: We identified two malignant cell populations, tumor stem cells and malignant carcinoma cells, and revealed two tumor progression pathways of SCNECC. By analyzing gene expression levels in the pathophysiology of SCNECC, we found that the expression levels of ERBB4 and NRG1, as well as the expression profile of mTOR signaling pathway mediated by them, were significantly upregulated in malignant carcinoma cells. In addition, we also found that carcinoma cells were able to stimulate malignant cell proliferation through the FN1 signaling pathway. The immune cells were in a stress state, with T-cell depletion, macrophage polarization, and mast cell glycolysis. These results suggested that carcinoma cells could interfere with immune response and promote tumor escape through MIF, TGFb, and other immunosuppressive-related signaling pathways.

Conclusion: This study revealed the mechanism of genesis and progression in SCNECC and the related important signaling pathways, such as mTOR, and provided new insights into the treatment of SCNECC.