Single cell RNA sequencing reveals the cytological characteristics and related immune microenvironment of gastric signet ring cell carcinoma

Abstract

BACKGROUND Gastric signet ring cell carcinoma (GSRC) is a special pathological type of gastric cancer (GC), which has the biological characteristics of high invasiveness, metastasis and poor prognosis, and has always been a major problem in clinical diagnosis and treatment. The current research on GSRC is stagnant at the tissue level of exome and mRNA sequencing, and lacks precision. We tried to use single-cell RNA sequencing (scRNA-seq)to reveal the biological characteristics of GSRC at the cellular level to guide clinical diagnosis and treatment, which has important theoretical and practical significance. METHODS We analyzed 32456 single cells from para-cancerous tissues of 5 patients and 117326 single cells from the cancer tissues of 13 patients by scRNA-seq. Results of the analysis were validated by immunohistochemistry, cell line cultures and bioinformatics. RESULTS The single-cell plot of GSRC was successfully constructed for the first time. There is also significant heterogeneity among Signet ring cell carcinoma (SRCC) sub-clusters. Microseminoprotein Beta (MSMB) as a marker can guide the identification of SRCC and moderate/poorly differentiated adenocarcinoma (M/PDA) cells. The up-regulated genes in SRCC were mainly enriched in abnormally active cancer-related signaling pathways and immune response signaling pathways. SRCC can be also significantly enriched in mitogen-activated protein kinases (MAPK) and estrogen signaling pathway, and they can interact and promote each other, and continue to amplify the effect. SRCC has lower cell adhesion and higher immune evasion ability, they also have an immunosuppressive microenvironment, these may be closely related to the relatively poor prognosis of GSRC. CONCLUSIONS Compared to M/PDA, GSRC has unique cytological characteristics and immune microenvironment, which will provide assistance for precision diagnosis and treatment.