The role of dynamic interplay exists between sympathetic and parasympathetic nerve in gastric tumorigenesis

作者：Diqun Chen, Xunjun Li, Yiyun Wang, Xinxin Li, Hongxia Zhang, Lína Zhang, Jia Yang, Haoyang Tan, Yingxin Xie, Yingyi Liuzhou, Jiayun Qiu, Miao Shi, Feiran Zhang, Wu Zhong, Kexing Xi, Chuanfa Fang, Alpha Ibrahima Balde, Jiang Yu, Tao Chen · 发表于：Interdisciplinary medicine · 年份：2024 · DOI：10.1002/inmd.20230040 · 被引用次数：5 · 研究领域：Cancer, Stress, Anesthesia, and Immune Response、Axon Guidance and Neuronal Signaling、Vagus Nerve Stimulation Research

Abstract Recent research underscores the significance of the nervous system in tumor progression. Nonetheless, understanding the intricate roles of nerves in gastric tumorigenesis remains limited. Our study aims to elucidate nerve alterations, associated key genes, and signaling pathways during gastric tumorigenesis. We enroll 257 patients with gastric precancerous lesions (GPLs) from four national cohorts. Utilizing immunohistochemistry and digital analysis, we quantified the densities of sympathetic and parasympathetic nerves, as well as Schwann cells in patient slides. We collected three mRNA expression profiles of GPL samples from the gene expression omnibus database and assessed them for nerve expression signatures, differentially expressed genes, enriched pathways, and the immune microenvironment. Parasympathetic nerve and Schwann cell densities display a progressive increase, while sympathetic nerve exhibits an inverse trend along the precancerous spectrums. Notably, CD8+ T cells, natural killer cells, and antigen‐presenting cells (APC) co‐inhibition decrease, while epithelial‐mesenchymal transition increases significantly from early to late premalignancy. Several key nerve‐regulating genes ( NTRK3 , MYBL2 , NRP1 , BCL2 , CCND1 , VEGFA , PLXNA2 , ADRB2 ), and pathways (mitogen‐activated protein kinase [MAPK]/ERK, PI3K/AKT, Wnt) emerge as potential contributors to precancerous progression. Our study reveals a dynamic relationship between sympathetic and parasympathetic ...