PD‐1 Coexpression Gene Analysis and the Regulatory Network in Endometrial Cancer Based on Bioinformatics Analysis

Abstract

Gynecological malignancies are tumors of the female reproductive system, mainly cervical cancer, endometrial cancer, and ovarian cancer. Endometrial cancer (EC) is the most common gynecological malignant tumor in developed countries. The aim of this study was to construct a network of programmed cell death protein 1 (PD-1) coexpressed genes through bioinformatics analysis and screen the potential biomarkers of PD-1 in endometrial cancer. In addition, genes and pathways involved in PD-1 and modulating tumor immune status were identified. We select the EC transcriptomic dataset in TCGA to retrieve gene sets on the cBioPortal platform, and the PD-1 coexpressed genes were obtained on the platform. GO and KEGG enrichment analysis of coexpressed genes was performed using the DAVID database. The target protein-protein interaction (PPI) network was constructed using Cytoscape 3.7.1 software, and the hub genes were then screened. A total of 976 coexpression genes were obtained. The enrichment analysis showed that PD-1 coexpressed genes were significantly enriched in overall components of the cell structure, the interaction of cytokines with cytokine receptors, chemokine signaling pathways, and cell adhesion molecules (CAMs). Ten hub genes were obtained by node degree analysis. CD3E gene is involved in the prognosis and immune process of EC, and the expression level is related to PD-1 (Pearson correlation coefficient is 0.82, P < 0.01 ). Patients with low CD3E gene expression in EC have a poor prognosis. The coexpression hub genes of PD-1 are related to immunity, in which CD3E is a prognostic marker that is involved in the PD-1/PD-L1-induced tumor immune escape. This study provides a new area to study the mechanism of PD-1/PD-L1 in EC and the precise treatment with targeted drugs.

Programmed Cell Death Ligand-1 (PDL-1) Correlates With Tumor Infiltration by Immune Cells and Represents a Promising Target for Immunotherapy in Endometrial Cancer

“…The factor interacts with the protein β-catenin which is responsible for cell motility and malignant signal transduction (26). Furthermore, bioinformatic analyses demonstrated that PD-1/PD-L1 signaling pathways crucially control chemokines and signaling and effector proteins of immune cells (27). According to the widely accepted molecular EC subtyping by The Cancer Genome Atlas (TCGA) group, four distinct molecular EC subtypes can be defined, implying different prognoses for patients (5).…”

Analysis of the characteristics of immune infiltration in endometrial carcinoma and its relationship with prognosis based on bioinformatics

“…[6,7] In addition, since the first Programmed Death 1/PD-L1 inhibitor was approved, many immune checkpoint inhibitors have also been used in clinic. [8] In the field of immunotherapy, Cytotoxic T-lymphocyte antigen 4 and Programmed Death 1 immune checkpoints have marked a paradigm shift. [9] Inhibitors of immune checkpoints target these molecules by alleviating certain inhibitory pathways, thereby promoting the immune system ability to combat tumors.…”

Bioinformatics Analysis of Immune Infiltration In Endometrial Carcinoma Tumors and its Relationship With Prognosis

“…The influence of immune-cell infiltration in tumors is very important, because the type of immune-cell infiltration in tumors mainly determines whether the balance tends to an anti-tumor or tumor-promotion immune response (7). Since the first PD-1/PD-L1 inhibitors were approved by the Food and Drug Administration (FDA) in 2014, many immune-checkpoint inhibitors have been used in clinical practice (8). Therefore, exploring the key immuneregulation genes and signaling pathways related to EC may clarify the critical molecular mechanisms of EC and improve the level of diagnosis and immunotherapy.…”