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

Diqun Chen; Xunjun Li; Yiyun Wang; Xinxin Li; Hongxia Zhang; Lina 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

doi:10.1002/INMD.20230040

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Interdisciplinary Medicine ›› 2024, Vol. 2 ›› Issue (2) : 20230040. DOI: 10.1002/INMD.20230040

RESEARCH ARTICLE

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

Diqun Chen¹^,² ,
Xunjun Li¹ ,
Yiyun Wang¹ ,
Xinxin Li² ,
Hongxia Zhang³ ,
Lina Zhang⁴ ,
Jia Yang⁵ ,
Haoyang Tan⁶ ,
Yingxin Xie⁷ ,
Yingyi Liuzhou⁸ ,
Jiayun Qiu⁶ ,
Miao Shi⁹ ,
Feiran Zhang²^,¹⁰ ,
Wu Zhong¹¹ ,
Kexing Xi¹^,¹¹ ,
Chuanfa Fang¹¹ ,
Alpha Ibrahima Balde¹² ,
Jiang Yu¹ ,
Tao Chen¹^,¹¹

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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 (mitogenactivated protein kinase [MAPK]/ERK, PI3K/AKT, Wnt) emerge as potential contributors to precancerous progression. Our study reveals a dynamic relationship between sympathetic and parasympathetic nerves, characterized by a gradual increase in parasympathetic nerve and Schwann cell density, contrasting with an inverse trend in sympathetic nerve across precancerous spectrums. Targeting the interaction between tumor cells and nerves, including sympathetic and parasympathetic nerves, has emerged as a promising strategy for the prevention and treatment of gastric cancer.

Keywords

bioinformatics / gastric precancerous lesion / immunohistochemistry / parasympathetic nerve / Schwann cell / sympathetic nerve

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Diqun Chen, Xunjun Li, Yiyun Wang, Xinxin Li, Hongxia Zhang, Lina 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. The role of dynamic interplay exists between sympathetic and parasympathetic nerve in gastric tumorigenesis. Interdisciplinary Medicine, 2024, 2(2): 20230040 https://doi.org/10.1002/INMD.20230040