EPHA3可能是一种新的预后生物标志物并与膀胱癌免疫浸润相关

2023年1月，汕头大学医学院第二附属医院泌尿外科;广州医科大学第五附属医院泌尿外科;中山大学第一附属医院泌尿外科 (Department of Urology, The Second Affiliated Hospital of Shantou University, Medical College,Shantou 515041, China；Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China；Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China) Hao Lin老师研究团队在《Cancers》上发表论文：

“EPHA3 Could Be a Novel Prognosis Biomarker and Correlates with Immune Infiltrates in Bladder Cancer"

“EPHA3可能是一种新的预后生物标志物并与膀胱癌免疫浸润相关"

Abstract：

Purpose: To assess the mechanism of EPH receptor A3 (EPHA3) and its potential value for immunotherapy in BLCA.

Materials and methods: The Cancer Genome Atlas (TCGA) bladder cancer (BLCA) database and the Gene Expression Omnibus (GEO) database were used for assessing whether EHPA3 could be used to predict BLCA prognosis. This work carried out in vitro and in vivo assays for exploring how EPHA3 affected the biological behaviors. The downstream pathway was explored using a Western blotting technique. The CIBERSORT, ESTIMATE, TIMER, and TIDE tools were used to predict the immunotherapy value of EPHA3 in BLCA.

Results: EPHA3 was poorly expressed in BLCA (p < 0.05), its high expression is related to a good survival prognosis (p = 0.027 and p = 0.0275), and it has a good predictive ability for the histologic grade and status of BLCA (area under curve = 0.787 and 0.904). Overexpressed EPHA3 could inhibit BLCA cell biological behaviors, and it be associated with the downregulation of the Ras/pERK1/2 pathway. EPHA3 was correlated with several immune-infiltrating cells and the corresponding marker genes.

Conclusions: EPHA3 could be regarded as an acceptable anti-cancer biomarker in BLCA. EPHA3 plays an inhibiting role in BLCA, and it could be the candidate immunotherapeutic target for BLCA.

摘要：

目的:探讨EPH受体A3 (EPHA3)的作用机制及其在BLCA免疫治疗中的潜在价值。材料与方法:采用Cancer Genome Atlas (TCGA)膀胱癌(BLCA)数据库和Gene Expression Omnibus (GEO)数据库评估EHPA3是否可用于预测BLCA预后。本工作通过体外和体内实验探讨EPHA3对生物行为的影响。使用Western blotting技术探索下游途径。采用CIBERSORT、ESTIMATE、TIMER和TIDE工具预测EPHA3在BLCA中的免疫治疗价值。结果:EPHA3在BLCA中表达较低(p < 0.05)，其高表达与较好的生存预后相关(p = 0.027和p = 0.0275)，对BLCA的组织学分级和状态有较好的预测能力(曲线下面积分别为0.787和0.904)。EPHA3过表达可抑制BLCA细胞的生物学行为，并与Ras/pERK1/2通路下调有关。EPHA3与多种免疫浸润细胞及相应的标记基因相关。结论:EPHA3可作为BLCA的一种可接受的抗癌生物标志物。EPHA3在BLCA中具有抑制作用，可能成为BLCA的候选免疫治疗靶点。

该论文中，人类膀胱癌细胞(5637、UMUC-3和T24)以及正常的人类尿上皮细胞(SVHUC)的体外培养是使用Ausbian特级胎牛血清完成的。