Pan-cancer analysis reveals BAF complexes as immune-related biomarkers and validation in triple-negative breast cancer

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-04-05 DOI:10.1016/j.lfs.2025.123607

Shuying Dai , Bei Li , Qingqian Wu , Shuang Han , Qingwen Zhao , Yule Wang , Yingjuan Zhang , Yue Gao

{"title":"Pan-cancer analysis reveals BAF complexes as immune-related biomarkers and validation in triple-negative breast cancer","authors":"Shuying Dai , Bei Li , Qingqian Wu , Shuang Han , Qingwen Zhao , Yule Wang , Yingjuan Zhang , Yue Gao","doi":"10.1016/j.lfs.2025.123607","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>BAF complexes (BAFs), ATP-dependent regulators of chromatin structure, play a significant role in cancer progression. This pan-cancer study aimed to decode the potential of specific BAFs in the pathology, immunity, and therapy of targeted cancers.</div></div><div><h3>Materials and methods</h3><div>Data were retrieved from The Cancer Genome Atlas, Gene Expression Omnibus, and IMvigor210 databases and were analyzed for expression patterns, prognostic value, mutational signatures, biological pathways, tumor immune microenvironment (TIME) remodeling, and therapeutic resistance of BAFs. Experimental validation was also conducted.</div></div><div><h3>Key findings</h3><div>BAFs exhibit abnormal expression in various human cancers. The BAFs model and nomogram (based on multiple variables) were developed as prognostic tools. BAFs regulate the TIME and influence the response to anti-PD-L1 therapy, particularly through ACTL6A, as observed in RNA sequencing and single-cell RNA sequencing datasets (high-resolution gene expression data at the single-cell level). ACTLA6 is a major adverse gene in the prognostic model. Patients with high ACTL6A expression showed significantly worse overall survival (hazard ratio = 1.32, 95 % CI: 1.26–1.39, <em>p</em> < 0.001). ACTL6A expression escalates with breast cancer (BRCA) malignancy, particularly in triple-negative BRCA (TNBC), and correlates with immune checkpoint expression while playing a crucial role in promoting cancer metastasis in TNBC.</div></div><div><h3>Significance</h3><div>Our findings first emphasize the significance of a novel BAFs model for patient prognosis and corroborate the considerable role of BAFs as immune-related biomarkers in pan-cancer progression. ACTL6A has a dual role as an immune-related biomarker and potential therapeutic target in TNBC, deepening our comprehension of its function as an oncogene.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123607"},"PeriodicalIF":5.2000,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525002413","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Aims

BAF complexes (BAFs), ATP-dependent regulators of chromatin structure, play a significant role in cancer progression. This pan-cancer study aimed to decode the potential of specific BAFs in the pathology, immunity, and therapy of targeted cancers.

Materials and methods

Data were retrieved from The Cancer Genome Atlas, Gene Expression Omnibus, and IMvigor210 databases and were analyzed for expression patterns, prognostic value, mutational signatures, biological pathways, tumor immune microenvironment (TIME) remodeling, and therapeutic resistance of BAFs. Experimental validation was also conducted.

Key findings

BAFs exhibit abnormal expression in various human cancers. The BAFs model and nomogram (based on multiple variables) were developed as prognostic tools. BAFs regulate the TIME and influence the response to anti-PD-L1 therapy, particularly through ACTL6A, as observed in RNA sequencing and single-cell RNA sequencing datasets (high-resolution gene expression data at the single-cell level). ACTLA6 is a major adverse gene in the prognostic model. Patients with high ACTL6A expression showed significantly worse overall survival (hazard ratio = 1.32, 95 % CI: 1.26–1.39, p < 0.001). ACTL6A expression escalates with breast cancer (BRCA) malignancy, particularly in triple-negative BRCA (TNBC), and correlates with immune checkpoint expression while playing a crucial role in promoting cancer metastasis in TNBC.

Significance

Our findings first emphasize the significance of a novel BAFs model for patient prognosis and corroborate the considerable role of BAFs as immune-related biomarkers in pan-cancer progression. ACTL6A has a dual role as an immune-related biomarker and potential therapeutic target in TNBC, deepening our comprehension of its function as an oncogene.

Abstract Image

查看原文本刊更多论文

泛癌分析显示BAF复合物是免疫相关的生物标志物，并在三阴性乳腺癌中得到验证。

目的：BAF复合物（BAF）是atp依赖的染色质结构调节因子，在癌症进展中起重要作用。这项泛癌症研究旨在解码特异性baf在靶向癌症的病理、免疫和治疗中的潜力。材料和方法：从The Cancer Genome Atlas、Gene Expression Omnibus和IMvigor210数据库中检索数据，分析baf的表达模式、预后价值、突变特征、生物学途径、肿瘤免疫微环境（TIME）重塑和治疗耐药性。并进行了实验验证。主要发现：BAFs在多种人类癌症中表现出异常表达。BAFs模型和nomogram（基于多个变量）被开发作为预后工具。正如在RNA测序和单细胞RNA测序数据集（单细胞水平的高分辨率基因表达数据）中观察到的那样，baf调节时间并影响抗pd - l1治疗的反应，特别是通过ACTL6A。ACTLA6是预后模型中的主要不良基因。ACTL6A高表达的患者总体生存期明显较差（风险比 = 1.32,95 % CI: 1.26-1.39, p ）意义：我们的研究结果首先强调了一种新的BAFs模型对患者预后的重要性，并证实了BAFs作为免疫相关生物标志物在泛癌症进展中的重要作用。ACTL6A在TNBC中具有免疫相关生物标志物和潜在治疗靶点的双重作用，加深了我们对其作为癌基因功能的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.