FCER1G positively relates to macrophage infiltration in clear cell renal cell carcinoma and contributes to unfavorable prognosis by regulating tumor immunity.
FCER1G positively relates to macrophage infiltration in clear cell renal cell carcinoma and contributes to unfavorable prognosis by regulating tumor immunity.
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DOI：
10.1186/s12885-022-09251-7
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发表时间：
2022-02-04
期刊：
影响因子：
3.8
通讯作者：
Cui X
中科院分区：
文献类型：
--
作者：
Dong K;Chen W;Pan X;Wang H;Sun Y;Qian C;Chen W;Wang C;Yang F;Cui X
肿瘤相关巨噬细胞（TAM）与肾透明细胞癌（ccRCC）患者的不良预后密切相关。然而，ccRCC和TAM之间相互作用的重要分子尚不清楚。比较肿瘤组织和癌旁正常组织的TCGA-KIRC基因表达数据，以鉴定ccRCC中差异表达的基因。通过分析这些差异表达基因与常见巨噬细胞生物标志物的相关性，发现TAMs相关基因。基因集富集分析预测TAMs相关基因的功能。使用从CheckMate 025研究获得的RNA测序数据和来自350名ccRCC患者样本的免疫组化分析进一步验证了这些发现。采用Kaplan-Meier生存曲线、考克斯回归分析和Harrell一致性指数分析判断预后。在这项研究中，我们应用生物信息学分析来探索在ccRCC中与TAM相关的差异表达基因，并确定了与所有选定的巨噬细胞生物标志物强烈相关的5个基因：STAC 3，LGALS 9，TREM 2，FCER 1G和PILRA。其中，FCER 1G在肿瘤组织中大量表达，并在接受Nivolumab治疗的ccRCC患者中显示出预后重要性;然而，在接受依维莫司治疗的患者中未显示出预后价值。我们还发现FCER 1G的高表达水平与T细胞抑制有关。此外，FCER 1G和巨噬细胞生物标志物CD 68的组合可以改善来自TCGA-KIRC的ccRCC患者的预后分层。基于对ccRCC患者样本的免疫组化分析，我们进一步验证了FCER 1G和CD 68在肿瘤组织中均高表达并且彼此相关。ccRCC组织中CD 68或FCER 1G的高表达表明总生存期和无进展生存期较短; CD 68和FCER 1G均高表达的患者预后最差。联合检测CD 68和FCER 1G有助于从同一TNM分期组中筛选出预后较差的患者。FCER 1G在ccRCC中的高表达与TAM浸润以及T细胞活化和增殖的抑制密切相关。结合FCER 1G和巨噬细胞生物标志物CD 68的表达水平可能是ccRCC患者有希望的术后预后指标。在线版本包含补充材料，可通过10.1186/s12885-022-09251-7获得。
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. 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. 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. High expression of FCER1G in ccRCC is closely related to TAMs infiltration and suppression of T cell activation and proliferation. Combining the expression levels of FCER1G and macrophage biomarker CD68 may be a promising postoperative prognostic index for patients with ccRCC. The online version contains supplementary material available at 10.1186/s12885-022-09251-7.
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DOI：
10.1056/nejmoa1510016
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Choueiri TK;Escudier B;Powles T;Mainwaring PN;Rini BI;Donskov F;Hammers H;Hutson TE;Lee JL;Peltola K;Roth BJ;Bjarnason GA;Géczi L;Keam B;Maroto P;Heng DY;Schmidinger M;Kantoff PW;Borgman-Hagey A;Hessel C;Scheffold C;Schwab GM;Tannir NM;Motzer RJ;METEOR Investigators
通讯作者：
METEOR Investigators
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
168.9
作者：
Rini, Brian I.;Powles, Thomas;Motzer, Robert J.
通讯作者：
Motzer, Robert J.
影响因子：
3.2
作者：
Naqvi, Afsar Raza;Fordham, Jezrom B.;Nares, Salvador
通讯作者：
Nares, Salvador