FCER1G Positively Relates To Macrophage Infiltration In Clear Cell Renal Cell Carcinoma And Contributes To Unfavorable Prognosis By Regulating Tumor Immunity

Abstract

Background: Tumor-associated macrophages (TAMs) are closely related to unfavorable prognosis of patients with clear cell renal cell carcinoma (ccRCC). However, the important molecules in the interaction between ccRCC and TAMs are unclear.Methods: TCGA-KIRC gene expression data of tumor tissues and normal tissues adjacent to tumor were compared to identify differentially expressed genes in ccRCC. TAMs related genes were discovered by analyzing the correlation between these differentially expressed genes and common macrophage biomarkers. Gene set enrichment analysis was performed to predict functions of TAMs related gene. The findings were further validated using RNA sequencing data obtained from the CheckMate 025 study and immunohistochemical analysis of samples from 350 patients with ccRCC. Kaplan–Meier survival curve, Cox regression analysis and Harrell’s concordance index analysis were used to determine the prognostic significance.Results: In this study, we applied bioinformatic analysis to explore TAMs related differentially expressed genes in ccRCC and identified 5 genes strongly correlated with all selected macrophage biomarkers: STAC3, LGALS9, TREM2, FCER1G, and PILRA. Among them, FCER1G was abundantly expressed in tumor tissues and showed prognostic importance in patients with ccRCC who received treatment with Nivolumab; however, it did not exhibit prognostic value in those treated with Everolimus. We also discovered that high expression levels of FCER1G are related to T cell suppression. Moreover, combination of FCER1G and macrophage biomarker CD68 can improve the prognostic stratification of patients with ccRCC from TCGA-KIRC. Based on the immunohistochemical analysis of samples from patients with ccRCC, we further validated that FCER1G and CD68 are both highly expressed in tumor tissue and correlate with each other. Higher expression of CD68 or FCER1G in ccRCC tissue indicates shorter overall survival and progression-free survival; patients with high expression of both CD68 and FCER1G have the worst outcome. Combining CD68 and FCER1G facilitates the screening of patients with a worse prognosis from the same TNM stage group.Conclusions: High expression of FCER1G in ccRCC is closely related to TAMs infiltration and suppression of T cell function. Combining the expression levels of FCER1G and macrophage biomarker CD68 may be a promising postoperative prognostic index for patients with ccRCC.

Identification and Analysis of Crucial Genes in H. pylori-Associated Gastric Cancer Using an Integrated Bioinformatics Approach

“…In addition, M2 macrophages can acquire their tumor suppressor function in part by suppressing cytotoxic T cells. Tis may explain the relevance of FCER1G to macrophage and T cell function [31]. Tese fndings were consistent with our results that high expression of FCER1G was positively correlated with infltration of M2 macrophages and negatively correlated with CD8 T cells.…”

TLR4 predicts patient prognosis and immunotherapy efficacy in clear cell renal cell carcinoma

“…TAMs have been shown to contribute to tumor development through a variety of mechanisms. In addition, TAMs are considered to reflect clinical outcome in ccRCC [50,51]. In this work, we also found that the expression of TLR4 is widely associated with the extent of macrophage infiltration (Figure 6C).…”