使用多组学分析鉴定 MCM6 在膀胱癌预后、免疫治疗反应和体外实验研究中的作用。
Identification of the role of MCM6 in bladder cancer prognosis, immunotherapy response, and in vitro experimental investigation using multi-omics analysis.
发表日期:2023 Nov 09
作者:
Jirong Wang, Xiaoran Li, Siyu Chen, Jinlong Cao, Xinpeng Fan, Huabin Wang, Xingxing Zhang, Li Yang
来源:
LIFE SCIENCES
摘要:
MCM6 在多种肿瘤中的促肿瘤作用已被广泛揭示,但其在膀胱癌 (BLCA) 中的具体作用仍不清楚。本研究的目的是探讨MCM6对BLCA的潜在影响。整合转录组和蛋白质组数据,通过加权基因共表达网络分析(WGCNA)和维恩分析确定MCM6与BLCA强相关。然后,利用公共数据库数据验证了MCM6的临床价值。在 MCM6 定义的亚组中也发现了不同的分子/免疫特征和免疫治疗的益处。此外,选择单细胞 RNA 测序 (scRNA-seq) 数据来量化不同 BLCA 细胞类型中的 MCM6 表达。通过体外功能实验评估MCM6的生物学作用,证明MCM6可以区分TCGA和GEO队列中的患者预后。此外,与MCM6低表达组相比,MCM6高表达组与更多的促肿瘤相关通路、侵袭性表型以及从免疫治疗中获益有关。 scRNA-seq数据分析发现MCM6主要表达于BLCA上皮细胞,且表达MCM6的肿瘤上皮细胞比例高于正常上皮细胞。此外,体外实验表明MCM6敲低可抑制BLCA细胞的增殖、细胞周期、迁移和侵袭。这项研究表明MCM6是一种有前途的预后和免疫治疗益处的标志物,可以促进BLCA细胞的增殖、侵袭和迁移。版权所有© 2023。由爱思唯尔公司出版。
The tumor-promoting effects of MCM6 in numerous tumors have been widely revealed, yet its specific role in bladder cancer (BLCA) is still elusive. The objective of this research was to explore the underlying impact of MCM6 on BLCA.Integrating transcriptomic and proteomic data, MCM6 was identified to be strongly correlated with BLCA through weighted gene co-expression network analysis(WGCNA) and venn analyses. Then, the clinical value of MCM6 was validated with public database data. The different molecular/immune characteristics and the benefit of immunotherapy were also found in MCM6-defined subgroups. Additionally, single-cell RNA sequencing (scRNA-seq) data was choose for quantify MCM6 expression in the distinct BLCA cell types. The biological role of MCM6 were evaluated via in vitro functional experiments.It was testified that the MCM6 could distinguish patients outcome in TCGA and GEO cohorts. Moreover, compared with the MCM6 low-expression group, the MCM6 high-expression group was related to more tumor-promoting related pathways, aggressive phenotypes, and benefit from immunotherapy. Analysis of scRNA-seq data resulted in MCM6 was mainly expressed in BLCA epithelial cells and the proportion of MCM6-expressing tumor epithelial cells is higher than the normal epithelial cells. Moreover, vitro experiments demonstrated that MCM6 knockdown repressed proliferation, cell cycle, migration, and invasion of BLCA cells.This research indicated MCM6 is a promising marker for both prognosis and immunotherapy benefit and could promote the cells proliferation, invasion and migration in BLCA.Copyright © 2023. Published by Elsevier Inc.