ZAP70 interaction with 13 mRNAs as a potential immunotherapeutic target for endometrial cancer.

Abstract

For advanced, refractory endometrial cancer (EC), it is advisable to find effective immunotherapeutic targets. In the present study, genes affecting the immune status of uterine corpus endometrial carcinoma (UCEC) samples within The Cancer Genome Atlas were explored by weighted correlation network analysis and differential gene expression analysis. The protein function and immune correlation of 14 key genes, including ζ-chain-associated protein kinase 70 (ZAP70), were analyzed. Based on the expression levels of key genes, the patients with UCEC were divided into two groups using consensus clustering, low expression (group 1) and high expression (group 2). Next, the functions of differentially expressed genes (DEGs) between the two groups were identified using Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes analysis and Gene Set Enrichment Analysis. The immune status of the patients in the two groups was evaluated using immune infiltration score and the expression levels of targets of immune checkpoint inhibitors. The role of ZAP70 in the prognosis of patients with UCEC and the differences in ZAP70 expression between EC tissues and healthy intimal tissues were determined by reverse transcription-quantitative PCR and immunohistochemistry. The present study found strong correlations between key genes, including ZAP70, LCK, FOXP3, TIGIT, CTLA4, ICOS, CD5, IL2RG, PDCD1, TNFRSF4, CD27, CCR7, GZMB, CXCL9. From the enrichment analyses, it was found that the functions of these DEGs were related to T cells. Patients in group 2 had stronger immune infiltration and higher immune checkpoints expression compared with those in group 1. ZAP70 was expressed at higher levels in EC tissues compared with in normal tissues, and may act as a protective factor in EC. In conclusion, ZAP70 interaction with 13 mRNAs may affect the immune status of patients with EC and may be a potential target for immunotherapy.