Critical Role of Guanylate Binding Protein 5 in Tumor Immune Microenvironment and Predictive Value of Immunotherapy Response

Overview

Journal Front Genet

Date 2022 Oct 17

PMID 36246628

Authors

Xiang Li

Dan Song

Song Su

Xiaobo He

Fengyu Cao

Chao Yang

Kai Li

Shuoyang Huang

Changhua Li

Chenhong Wang

Aikang Zhang

Pengcheng Pang

Yongbin Zheng

Affiliations

Soon will be listed here.

Abstract

The guanylate-binding proteins (GBPs) are the latest potential targets of immunotherapy. However, the role of GBP5 in pan-cancer, including colorectal cancer (CRC), remains unclear. This study aims to explore the effect of GBP5 on immunity in pan-cancer. Based on the RNA sequencing data of 33 cancers obtained from The Cancer Genome Atlas, we analyzed the clinical significance of GBPs and focused on the correlation between GBP5 and tumor microenvironment (TME). Immunotherapy cohort IMvigor210 was used to explore the relationship between treatment response and GBPs. Then, we further analyzed the expression of GBP5 in immune cells using single-cell transcriptome cohort GSE146771 and GSE132465 from the Gene Expression Omnibus database. Finally, a prognostic model based on GBP5 expression was established and validated. We found that the expression of GBP3/4/5 is higher in colorectal cancer than in normal tissues, and GBP5 is a better predictor of good treatment response to immune checkpoint blockade than other GBPs. In most other cancers, GBP5 is also elevated in tumors compared with normal tissues and is associated with a better prognosis. As for TME, GBP5 is generally positively correlated with immune score, the level of tumor-infiltrating immune cells and immune-related genes. Single-cell analysis showed that GBP5 was mainly expressed in myeloid cells and T cells. The GBP5-related prognostic model we constructed in CRC can predict the survival of patients and propose some genes for subsequent research. This study revealed a strong correlation between GBP5 and immunity in generalized cancer and provided evidence that CRC may be a suitable cancer type for anti-GBP5 therapy.

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