← 返回

SIRT1 在泛癌中的预后、免疫和诊断作用的综合分析及其在 KIRC 中的验证

英文原题:Comprehensive analysis of the prognostic, immunological, and diagnostic roles of SIRT1 in pan-cancer and its validation in KIRC.

查看英文原题

Comprehensive analysis of the prognostic, immunological, and diagnostic roles of SIRT1 in pan-cancer and its validation in KIRC.

PubMed 2025/01/08(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

采用生物信息学分析与实验验证相结合的综合方法,我们阐明了 SIRT1 在泛癌中的潜在作用及机制,为 SIRT1 靶向疗法在临床应用中的开发提供了理论依据。

研究思路结论见上方概要

DNA损伤修复的紊乱可能导致癌症。SIRT1是一种NAD+依赖性去乙酰化酶,通过调节组蛋白翻译后修饰、DNA修复和细胞代谢等过程,在维持细胞稳态中发挥关键作用。然而,目前仍缺乏对SIRT1在泛癌中作用的全面探索。本研究旨在分析SIRT1在泛癌中的作用,以更全面地了解其在多种恶性肿瘤中的作用。

我们通过分析癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库的数据,系统性地研究了SIRT1在泛癌中的作用。使用包括R、Cytoscape、HPA、Archs4、TISIDB、cBioPortal、STRING、GSCALite和CancerSEA在内的多种工具,整合并分析了SIRT1基因表达、预后、蛋白质相互作用、信号通路、免疫浸润及其他相关信息。此外,我们通过实验验证了SIRT1在正常人肾细胞和肾癌细胞系中的差异表达。

SIRT1 在多种癌症中表达显著降低,且在不同分子和免疫亚型间存在差异。SIRT1 与众多癌症通路存在复杂关联。在大多数癌症类型中,SIRT1 表达升高与嗜酸性粒细胞、辅助性 T 细胞、中枢记忆 T 细胞、效应记忆 T 细胞、γδ T 细胞和 Th2 细胞呈正相关。SIRT1 表达在多种癌症类型中与免疫调节因子显著相关。定量逆转录聚合酶链反应(qRT-PCR)和 Western blot(WB)分析证实,SIRT1 在肾透明细胞癌(KIRC)中差异表达。

展开英文摘要原文

Disturbances in DNA damage repair may lead to cancer. SIRT1, an NAD+-dependent deacetylase, plays a crucial role in maintaining cellular homeostasis through the regulation of processes such as histone posttranslational modifications, DNA repair, and cellular metabolism. However, a comprehensive exploration of SIRT1's involvement in pan-cancer remains lacking. Our study aimed to analyze the role of SIRT1 in pan-cancer to gain a more comprehensive understanding of its role in multiple malignancies.

We systematically examined the role of SIRT1 in pan-cancer by analyzing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Various tools, including R, Cytoscape, HPA, Archs4, TISIDB, cBioPortal, STRING, GSCALite, and CancerSEA, were used to integrate and analyze SIRT1 gene expression, prognosis, protein interactions, signaling pathways, immune infiltration, and other relevant information. Furthermore, we validated the differential expression of SIRT1 in normal human kidney cells and kidney cancer cell lines via experimental verification.

SIRT1 expression was significantly reduced in various cancers and was different across molecular and immune subtypes. SIRT1 is intricately linked to numerous cancer pathways. In most cancer types, increased SIRT1 expression is positively associated with eosinophils, helper T cells, central memory T cells, effector memory T cells, γδ T cells, and Th2 cells. SIRT1 expression is significantly correlated with immune regulatory factors across various cancer types. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) analyses confirmed that SIRT1 is differentially expressed in kidney renal clear cell carcinoma (KIRC).

Using an integrative approach involving bioinformatics analysis and experimental validation, we clarified the potential roles and mechanisms of SIRT1 in pan-cancer, providing a theoretical basis for the development of SIRT1-targeted therapies in clinical applications.

论文信息

作者
Liu Q、Sun S、Zhou C、Xu H
单位
School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.China
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 39845948 · DOI 10.3389/fimmu.2024.1501867