Profiles of PD-1, PD-L1, PD-L2 in Gastric Cancer and Their Relation with Mutation, Immune Infiltration, and Survival.

Jingwei Liu,Hao Li,Liping Sun,Yuan Yuan,Chengzhong Xing

doi:10.1155/2020/2496582

Abstract

Background Although multiple types of cancers demonstrated favorable outcome after immunotherapy of PD-1/PD-L1 blockade, the specific regulatory mechanism of PD genes in gastric cancer (GC) remains largely unknown. Materials and Methods Expression of RNA, copy number variants, and clinical parameters of GC individuals from TCGA were analyzed. Coexpressed genes for PD-1, PD-L1, and PD-L2 were selected by correlation analysis and confirmed by STRING. Gene Ontology and KEGG pathway analyses were performed by clusterProfiler. The influence of PD-1/PD-L1/PD-L2 on immune cell infiltration was investigated by MCP-counter. Results PD-L2 demonstrated significant relation with clinical stage of GC (P = 0.043). Survival analysis showed that PD-1 expression was correlated with better prognosis of GC patients (HR = 0.70, P = 0.031), but PD-L2 expression was related with worse survival (HR = 1.42, P = 0.032). Mutation of PIK3CA could alter the level of PD-1, PD-L1, and PD-L2 (P < 0.001), and TP53 mutation demonstrated significant correlation with PD-L1 (P = 0.015) and PD-L2 (P = 0.014) expression. Enrichment analysis of PD-1/PD-L1/PD-L2 coexpressed genes indicated a biological process of mononuclear cell proliferation, leukocyte cell-cell adhesion, and lymphocyte activation as well as KEGG pathways including cell differentiation of Th1 and Th2, cell differentiation of Th17, and hematopoietic cell landscape. As for immune infiltration analysis, PD-1 was mainly related with cytotoxic lymphocytes and endothelial cells; PD-L1 were associated with monocytic lineage; PD-L2 showed significant correlation with myeloid dendritic cells. Conclusion PD-1 expression showed association with better prognosis of GC, and PD-L2 expression was related with worse survival. Mutations of PIK3CA and TP53 significantly correlated with PD-1/PD-L1/PD-L2 axis. PD-1/PD-L1/PD-L2 coexpressed genes demonstrated enrichment in mononuclear cell proliferation, leukocyte cell-cell adhesion, and lymphocyte activation as well as KEGG pathways including cell differentiation of Th1, Th2, and Th17.

Highlights

Gastric cancer (GC) is a refractory cancer in the human upper digestive system; the incidence and mortality of which remain relatively high all around the world [1, 2]
Programmed death 1 (PD-1) and its ligands programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) serve as an immune checkpoint axis which can be utilized by cancer cells for immune escape from destruction by T cells [9, 10]
PD-L2 was associated with clinical stage (P = 0:043), while no significant relation was observed for PD-1 (P = 0:073) and PD-L1 (P = 0:316) (Figure 1(b))

Summary

Introduction

Gastric cancer (GC) is a refractory cancer in the human upper digestive system; the incidence and mortality of which remain relatively high all around the world [1, 2]. Multiple types of cancers demonstrated favorable outcome after immunotherapy of PD-1/PD-L1 blockade, the specific regulatory mechanism of PD genes in gastric cancer (GC) remains largely unknown. Enrichment analysis of PD-1/PD-L1/PD-L2 coexpressed genes indicated a biological process of mononuclear cell proliferation, leukocyte cell-cell adhesion, and lymphocyte activation as well as KEGG pathways including cell differentiation of Th1 and Th2, cell differentiation of Th17, and hematopoietic cell landscape. As for immune infiltration analysis, PD-1 was mainly related with cytotoxic lymphocytes and endothelial cells; PD-L1 were associated with monocytic lineage; PD-L2 showed significant correlation with myeloid dendritic cells. PD-1/PD-L1/PD-L2 coexpressed genes demonstrated enrichment in mononuclear cell proliferation, leukocyte cell-cell adhesion, and lymphocyte activation as well as KEGG pathways including cell differentiation of Th1, Th2, and Th17

Methods

Results

Discussion

Conclusion