EPHA3可能是一種新的預后生物標志物并與膀胱癌免疫浸潤相關

2023年1月，汕頭大學醫學院第二附屬醫院泌尿外科;廣州醫科大學第五附屬醫院泌尿外科;中山大學第一附屬醫院泌尿外科 (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老師研究團隊在《Cancers》上發表論文：

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

“EPHA3可能是一種新的預后生物標志物并與膀胱癌免疫浸潤相關"

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:探討EPH受體A3 (EPHA3)的作用機制及其在BLCA免疫治療中的潛在價值。材料與方法:采用Cancer Genome Atlas (TCGA)膀胱癌(BLCA)數據庫和Gene Expression Omnibus (GEO)數據庫評估EHPA3是否可用于預測BLCA預后。本工作通過體外和體內實驗探討EPHA3對生物行為的影響。使用Western blotting技術探索下游途徑。采用CIBERSORT、ESTIMATE、TIMER和TIDE工具預測EPHA3在BLCA中的免疫治療價值。結果:EPHA3在BLCA中表達較低(p < 0.05)，其高表達與較好的生存預后相關(p = 0.027和p = 0.0275)，對BLCA的組織學分級和狀態有較好的預測能力(曲線下面積分別為0.787和0.904)。EPHA3過表達可抑制BLCA細胞的生物學行為，并與Ras/pERK1/2通路下調有關。EPHA3與多種免疫浸潤細胞及相應的標記基因相關。結論:EPHA3可作為BLCA的一種可接受的抗癌生物標志物。EPHA3在BLCA中具有抑制作用，可能成為BLCA的候選免疫治療靶點。

該論文中，人類膀胱癌細胞(5637、UMUC-3和T24)以及正常的人類尿上皮細胞(SVHUC)的體外培養是使用Ausbian特級胎牛血清完成的。