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预后生物标志物CPEB3及其与透明细胞肾细胞癌免疫浸润的关联。

Prognostic biomarker CPEB3 and its associations with immune infiltration in clear cell renal cell carcinoma.

作者信息

Hong Hualan, Shi Xi, Ou Wenyong, Ou Pengju

机构信息

Department of Medical Oncology, Cancer Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350000, P.R. China.

Department of Medical Oncology, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350000, P.R. China.

出版信息

Biomed Rep. 2024 Feb 19;20(4):63. doi: 10.3892/br.2024.1751. eCollection 2024 Apr.

Abstract

The role and underlying mechanism of cytoplasmic polyadenylation element binding protein 3 (CPEB3) in clear cell renal cell carcinoma [ccRCC progression remain poorly characterized. The present study was designed to evaluate the role of CPEB3 in ccRCC and its clinical associations. The overall response rate of first-line therapies (ICIs combined with VEGFR-TKIs or ICI combination) for ccRCC] is 42.0-59.3%, so a number of patients with ccRCC do not benefit from these therapies. To avoid immunosurveillance and immune killing, tumor cells decrease immunogenicity and recruit immunosuppressive cells such as regulatory T cells (Tregs). Tregs inhibit the development of anti-tumor immunity, thereby hindering immune surveillance of cancer and preventing effective anti-tumor immune response in tumor-bearing hosts. The present study analyzed clinical specimens from patients ccRCC and then examined the role of CPEB3 in ccRCC via bioinformatics analysis. CPEB3 expression was significantly reduced in ccRCC compared with normal tissue and low CPEB3 expression was associated with poor overall survival. Moreover, CPEB3 expression was an independent predictor of survival. CPEB3 expression was positively associated with immune biomarkers [CD274, programmed cell death 1 ligand 2, Hepatitis a virus cellular receptor 2, Chemokine (C-X-C motif) ligand (CXCL)9, CXCL10, Inducible T cell costimulatory, CD40, CD80 and CD38] that improve the outcome of anti-tumor immune responses. CPEB3 expression in ccRCC also affected the status of 24 types of infiltrating immune cell, of which Tregs were the most significantly negatively correlated cell type. CPEB3 may serve as a prognostic biomarker in ccRCC and its mechanism may be related to the regulation of Tregs.

摘要

细胞质聚腺苷酸化元件结合蛋白3(CPEB3)在肾透明细胞癌(ccRCC)进展中的作用及潜在机制仍未得到充分阐明。本研究旨在评估CPEB3在ccRCC中的作用及其临床相关性。ccRCC一线治疗(免疫检查点抑制剂[ICIs]联合血管内皮生长因子受体酪氨酸激酶抑制剂[VEGFR-TKIs]或ICI联合治疗)的总缓解率为42.0%-59.3%,因此许多ccRCC患者无法从这些治疗中获益。为了避免免疫监视和免疫杀伤,肿瘤细胞降低免疫原性并招募免疫抑制细胞,如调节性T细胞(Tregs)。Tregs抑制抗肿瘤免疫的发展,从而阻碍对癌症的免疫监视并阻止荷瘤宿主产生有效的抗肿瘤免疫反应。本研究分析了ccRCC患者的临床标本,然后通过生物信息学分析研究CPEB3在ccRCC中的作用。与正常组织相比,CPEB3在ccRCC中的表达显著降低,且CPEB3低表达与较差的总生存期相关。此外,CPEB3表达是生存的独立预测指标。CPEB3表达与免疫生物标志物[CD274、程序性细胞死亡1配体2、甲型肝炎病毒细胞受体2、趋化因子(C-X-C基序)配体(CXCL)9、CXCL10、诱导性T细胞共刺激分子、CD40、CD80和CD38]呈正相关,这些生物标志物可改善抗肿瘤免疫反应的结果。CPEB3在ccRCC中的表达还影响24种浸润免疫细胞的状态,其中Tregs是相关性最显著的负性细胞类型。CPEB3可能作为ccRCC的预后生物标志物,其机制可能与Tregs的调节有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f246/10928475/5d2cafc5440f/br-20-04-01751-g00.jpg

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