PLXDC1 Can Be a Biomarker for Poor Prognosis and Immune Evasion in Gastric Cancer

Xinwei Li,1,* Yongfei Fan,2,* Mingyue Tang,1 Huiyuan Li,1 Yue Zhang,1 Jiaqi Mi,1 Yanyan Wang,1 Menglin Zhao,1 Zishu Wang,1 Fang Su1 1Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China; 2Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang Su; Zishu Wang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China, Tel +86 13605523272; +86 13955254185, Email sufang@bbmc.edu.cn; wzshahbb@163.comBackground: Research has revealed that Plexin domain containing 1 (PLXDC1) is correlated with the prognosis of a variety of tumors, but its role in the tumor microenvironment (TME) of gastric cancer has not been reported.Methods: In this study, we analyzed PLXDC1 expression in gastric cancer using the Oncomine and the Cancer Genome Atlas (TCGA) databases and immunohistochemical staining experiments, and performed prognostic assessment with data from the TCGA and Kaplan–Meier Plotter databases. The immunomodulatory role of PLXDC1 in the gastric cancer TME was analyzed by signaling pathway enrichment, immune cell correlation analysis, immunomodulator risk model construction and immunohistochemical staining experiments of immune cells.Results: The results indicated that PLXDC1 was overexpressed in gastric cancer and that its overexpression was associated with poor prognosis. Multivariate Cox analysis revealed that PLXDC1 could be an independent biomarker of the risk of gastric cancer. Signaling pathway enrichment revealed that high PLXDC1 expression was involved in signaling pathways related to immune activation and stromal activation, and Tumor Immune Dysfunction and Exclusion (TIDE) assessment indicated that high PLXDC1 expression was associated with a significantly higher risk of immune evasion than low PLXDC1 expression. A Cox risk model based on PLXDC1-associated immunomodulators also presented poor prognosis, and immune evasion was significantly higher in the high-risk group than in the low-risk group. In addition, immunohistochemical staining of CD8/CD3/CD4+ T cells in the high and low PLXDC1 expression groups also observed immune cell distribution characteristics of immune evasion.Conclusion: This study analyzed PLXDC1 from multiple biological perspectives and revealed that PLXDC1 can be a biomarker for poor prognosis and immune evasion in gastric cancer.Graphical Abstract: Keywords: PLXDC1, biomarker, tumor microenvironment, immune evasion, prognosis, immunotherapy