解析膀胱癌中 anoikis 的意义及 S100A7 作为潜在治疗靶点的系统分析。

Deciphering the significance of anoikis in bladder cancer and systematic analysis of S100A7 as a potential therapeutic target.

机构信息

Department of Urology, Institute of Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, 9 DongDan SANTIAO, Beijing, 100730, China.

出版信息

Eur J Med Res. 2024 Jan 12;29(1):52. doi: 10.1186/s40001-024-01642-9.

DOI:10.1186/s40001-024-01642-9

PMID:38217031

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10785515/

Abstract

BACKGROUND

Bladder cancer is an epidemic and life-threating urologic carcinoma. Anoikis is a unusual type of programmed cell death which plays a vital role in tumor survival, invasion and metastasis. Nevertheless, the relationship between anoikis and bladder cancer has not been understood thoroughly.

METHODS

We downloaded the transcriptome and clinical information of BLCA patients from TCGA and GEO databases. Then, we analyzed different expression of anoikis-related genes and established a prognostic model based on TCGA database by univariate Cox regression, lasso regression, and multivariate Cox regression. Then the Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were performed. GEO database was used for external validation. BLCA patients in TCGA database were divided into two subgroups by non-negative matrix factorization (NMF) classification. Survival analysis, different gene expression, immune cell infiltration and drug sensitivity were calculated. Finally, we verified the function of S100A7 in two BLCA cell lines.

RESULTS

We developed a prognostic risk model based on three anoikis-related genes including TPM1, RAC3 and S100A7. The overall survival of BLCA patients in low-risk groups was significantly better than high-risk groups in training sets, test sets and external validation sets. Subsequently, the checkpoint and immune cell infiltration had significant difference between two groups. Then we identified two subtypes (C and C) through NMF analysis and found CA had better OS and PFS than CB. Besides, the accuracy of risk model was verified by ROC analysis. Finally, we identified that knocking down S100A7 gene expression restrained the proliferation and invasion of bladder cancer cells.

CONCLUSION

We established and validated a bladder cancer prognostic model consisting of three genes, which can effectively evaluate the prognosis of bladder cancer patients. Additionally, through cellular experiments, we demonstrated the significant role of S100A7 in the metastasis and invasion of bladder cancer, suggesting its potential as a novel target for future treatments.

摘要

背景

膀胱癌是一种流行且危及生命的泌尿系统癌。细胞凋亡是一种异常的程序性细胞死亡，在肿瘤的存活、侵袭和转移中起着至关重要的作用。然而，细胞凋亡与膀胱癌之间的关系尚未被充分理解。

方法

我们从 TCGA 和 GEO 数据库中下载了膀胱癌患者的转录组和临床信息。然后，我们分析了不同的细胞凋亡相关基因的表达，并基于 TCGA 数据库通过单变量 Cox 回归、lasso 回归和多变量 Cox 回归建立了一个预后模型。然后进行 Kaplan-Meier 生存分析和接收者操作特征（ROC）曲线分析。GEO 数据库用于外部验证。TCGA 数据库中的膀胱癌患者通过非负矩阵分解（NMF）分类分为两个亚组。计算生存分析、不同基因表达、免疫细胞浸润和药物敏感性。最后，我们在两个膀胱癌细胞系中验证了 S100A7 的功能。

结果

我们基于三个细胞凋亡相关基因（TPM1、RAC3 和 S100A7）建立了一个预后风险模型。低风险组的膀胱癌患者在训练集、测试集和外部验证集中的总生存期明显长于高风险组。随后，两组之间的检查点和免疫细胞浸润有显著差异。然后我们通过 NMF 分析确定了两个亚型（C 和 C），并发现 CA 比 CB 具有更好的 OS 和 PFS。此外，风险模型的准确性通过 ROC 分析得到验证。最后，我们确定敲低 S100A7 基因表达可抑制膀胱癌细胞的增殖和侵袭。