研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

通过生物信息学和实验分析鉴定和验证膀胱癌中唾液酸转移酶 ST3Gal5。

Identification and validation of sialyltransferase ST3Gal5 in bladder cancer through bioinformatics and experimental analysis.

发表日期:2024 Jul 02
作者: Yuli Jian, Qiwei Chen, Abdullah Al-Danakh, Zhongyang Xu, Chunyan Xu, Xiaoxin Sun, Xiao Yu, Deyong Yang, Shujing Wang
来源: Cellular & Molecular Immunology

摘要:

膀胱癌(BLCA)是世界上十大最常见癌症之一。异常唾液酸化是肿瘤发生和肿瘤免疫的一个常见特征。本研究旨在探讨唾液酸转移酶 ST3Gal5 对 BLCA 的潜在影响。最初,在 TCGA-BLCA 队列中使用多种生物信息学方法鉴定了糖基转移酶相关 DEG (GRDEG),并使用 GEO 数据库进行了验证。采用单变量和多变量 Cox 回归分析,临床预后整合有助于将 ST3Gal5 确定为 BLCA 的独立预后因素。通过 CIBERSORT 和 ssGSEA 分析评估免疫细胞浸润,同时评估低 ST3Gal5 组和高 ST3Gal5 组的 HLA 和免疫检查点基因水平以及药物敏感性。 TIDE 和 IPS 评分用于衡量免疫检查点封锁 (ICB) 反应。此外,还进行了体内和体外功能实验,以阐明 ST3Gal5 的生物学作用。与生物信息学研究结果一致,ST3Gal5 表达在 BLCA 组织和细胞中下调,与较差的预后结果相关。低 ST3Gal5 组的 StromalScore、ImmuneScore 和 ESTIMATEScore 显着升高。此外,低ST3Gal5组的HLA和免疫检查点基因水平上调。下调的 ST3Gal5 在体内和体外促进 BLCA 细胞的增殖、迁移和侵袭。我们的研究结果表明,低 ST3Gal5 水平促进 BLCA 的肿瘤发生和进展,暗示其作为预测生物标志物和治疗靶点的潜力。版权所有 © 2024 Elsevier B.V.保留所有权利。
Bladder cancer (BLCA) is one of the top ten most common cancers in the world. Aberrant sialylation is a common feature in tumorigenesis and tumor immunity. This study seeks to explore the potential impact of sialyltransferase ST3Gal5 on BLCA.Initially, glycosyltransferase-related DEGs (GRDEGs) were identified using multiple bioinformatics approaches in TCGA-BLCA cohort and validated using GEO databases. Clinical prognosis integration facilitated the determination of ST3Gal5 as an independent prognostic factor in BLCA, employing univariate and multivariate Cox regression analyses. Immune cell infiltration was assessed via CIBERSORT and ssGSEA analyses, while HLA and immune checkpoint genes' levels, along with drug sensitivity, were evaluated in low- and high-ST3Gal5 groups. The TIDE and IPS scores were used to gauge the immune checkpoint blockade (ICB) response. Furthermore, functional experiments, both in vivo and in vitro, were conducted to elucidate the biological roles of ST3Gal5.In agreement with bioinformatics findings, ST3Gal5 expression was down-regulated in BLCA tissues and cells, correlating with poorer prognostic outcomes. The StromalScore, ImmuneScore, and ESTIMATEScore were significantly elevated in low-ST3Gal5 group. Moreover, the levels of HLA and immune checkpoint genes were upregulated in low-ST3Gal5 group. Down-regulated ST3Gal5 promoted the proliferation, migration, and invasion of BLCA cells in vivo and in vitro.Our findings demonstrated that low ST3Gal5 level promoted tumorigenesis and progression of BLCA, implying its potential as a predictive biomarker and therapeutic target.Copyright © 2024 Elsevier B.V. All rights reserved.