Lamin B2 is highly expressed in gastric cancer and regulates the immune microenvironment
ZENG Wen1,LIN Zhongnan2, GUO Pengkun1, LIN Lizhi3, LIN Kezhi1, CHEN Xiaodong4, XUE Xiangyang1.
1.Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Wenzhou Medical University,Wenzhou 325035, China; 2.Department of Sports Medicine, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; 3.Department of Gastrointestinal Surgery,the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027,China; 4.Department of Gastrointestinal Surgery, the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015, China
ZENG Wen,LIN Zhongnan,GUO Pengkun, et al. Lamin B2 is highly expressed in gastric cancer and regulates the immune microenvironment[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(7): 539-546,553.
Abstract：Objective: To investigate the expression characteristics of lamin B2 (LMNB2) in patients with gastric cancer and its correlation with clinical prognosis and clinicopathological features, to explore the effect of LMNB2 on immune microenvironment of gastric cancer. Methods: A unified and standardized pan-cancer dataset was downloaded from UCSC database to analyze the expression of LMNB2 in 19 131 normal tissues adjacent to cancer and 60 499 tumor tissues. A total of 142 gastric cancer tissues and 28 paracancer normal tissues that underwent radical resection of gastric cancer in the First Affiliated Hospital of Wenzhou Medical University from 2014 to 2016 were collected. The differential expression of LMNB2 in 127 gastric cancer tissues and 28 paracancerous tissues was detected by immunohistochemistry. The relationship between the expression of LMNB2 and the prognosis and clinicopathological features of patients were analyzed combined with clinical information.The ESTIMATE algorithm was used to analyze the effect of LMNB2 expression level on matrix and immune cell infiltration in gastric cancer tissues. The infiltration of different immune cells in gastric cancer tissues and the correlation between tumor mutation burden (TMB), microsatellite instability (MSI), programmed cell death 1 ligand 1 (PD-L1) and LMNB2 expression levels were analyzed, and the clinical tissue samples were further verified and analyzed. Results: The expression of LMNB2 was up-regulated in gastric cancer tissues, which was associated with poor prognosis and worse TNM stage of patients. The ESTIMATE analysis showed that the expression of LMNB2 was negatively correlated with immune score (r=-0.202, P<0.001), matrix score (r=-0.272,P<0.001) and ESTIMATE score (r=-0.251, P<0.001). Analysis of the infiltration of immune cells showed that the expression of LMNB2 was significantly positively correlated with the infiltration of M1 macrophages (r=0.322,P<0.001), NK cells (r=0.423, P<0.001) and neutrophils (r=0.307, P<0.001). Furthermore, immunohistochemical analysis of tissue chips showed that the high expression group of LMNB2 had higher CD4 (P<0.05) and CD56 (P<0.05) scores, but lower CD8 (P<0.05) and CD163 (P<0.01) scores. The expression level of LMNB2 was significantly positively correlated with TMB scores (r=0.343, P<0.001) and MSI scores (r=0.221, P<0.001) in gastric cancer, and the expression of PD-L1 in the high expression group of LMNB2 was up-regulated (P<0.05).Conclusion: The up-regulated expression of LMNB2 in gastric cancer regulates the immune microenvironment in gastric cancer, which may be a potential diagnostic marker for gastric cancer and an indicator to evaluate the efficacy of immune checkpoint inhibitors in patients with gastric cancer.
