TNIP1通过调节BRCA的免疫微环境影响预后。

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2026-02-01 Epub Date: 2025-01-27 DOI:10.1007/s10528-025-11034-1
Dong Liao, Wu Liu, Yunhui Jiang, Ping Zhao, Yun Yao
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引用次数: 0

摘要

乳腺浸润性癌(BRCA)影响着全世界的女性,尽管在诊断、预防和治疗方面取得了进展,但结果仍然不理想。TNIP1是一个涉及多种免疫信号通路的新靶点,影响肿瘤的发展和生存。然而,BRCA和TNIP1之间的联系尚不清楚。来自TCGA、GEO、Sangerbox和alcan数据库的数据分析显示,TNIP1在BRCA组织中表达过低。RT-PCR和免疫组织化学证实了这一发现。此外,来自TCGA和GEPIA2数据库以及Sangerbox的数据确定TNIP1是BRCA患者预后不良的标志。TNIP1表达与BRCA肿瘤微环境(TME) StromalScore (R = 0.22)、ImmuneScore (R = 0.25)、ESTIMATEScore (R = 0.27)呈显著正相关。各种算法已经证明了TNIP1表达与BRCA肿瘤浸润免疫细胞(TIICs)之间的强烈关联。使用EPIC、TIMER、MCPCounter、QUANTISEQ、xCell和其他计算工具进一步分析显示,TNIP1表达升高与免疫细胞评分升高显著相关。TNIP1在BRCA肿瘤组织中的表达也与免疫检查点标志物有很强的相关性。来自HAP数据库的数据表明,TNIP1的表达主要参与正常皮肤微环境。随后使用TISCH平台和BRCA单细胞数据集进行的分析表明,与BRCA患者的非免疫细胞相比,TNIP1在免疫细胞中的表达水平更高。该表达与TME内炎症(R = 0.25)、分化(R = 0.28)呈显著正相关,与BRCA干性(R = - 0.34)、侵袭性(R = - 0.22)呈负相关。因此,TNIP1被认为是BRCA的潜在预后标志物和治疗靶点。
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TNIP1 Impacts Prognosis by Modulating the Immune Microenvironment in BRCA.

Breast invasive carcinoma (BRCA) affects women worldwide, and despite advancements in diagnosis, prevention, and treatment, outcomes remain suboptimal. TNIP1, a novel target involved in multiple immune signaling pathways, influences tumor development and survival. However, the connection between BRCA and TNIP1 remains unclear. Analysis of data from the TCGA, GEO, Sangerbox, and Ualcan databases revealed that TNIP1 is underexpressed in BRCA tissues. This finding was corroborated by RT-PCR and immunohistochemistry. Furthermore, data from the TCGA and GEPIA2 databases, along with Sangerbox, identified TNIP1 as a marker of poor prognosis in BRCA patients. TNIP1 expression shows significant positive correlations with the BRCA Tumor Microenvironment (TME) StromalScore (R = 0.22), ImmuneScore (R = 0.25), and ESTIMATEScore (R = 0.27). Various algorithms have demonstrated a strong association between TNIP1 expression and BRCA tumor-infiltrating immune cells (TIICs). Further analysis using EPIC, TIMER, MCPCounter, QUANTISEQ, xCell, and other computational tools revealed that elevated TNIP1 expression is significantly associated with increased immune cell scores. TNIP1 expression in BRCA tumor tissues also shows a strong correlation with immune checkpoint markers. Data from the HAP database indicate that TNIP1 expression is predominantly involved in the normal skin microenvironment. Subsequent analysis using the TISCH platform with the BRCA single-cell dataset demonstrated that TNIP1 exhibits higher expression levels in immune cells compared to non-immune cells in BRCA patients. This expression is significantly positively correlated with inflammation (R = 0.25) and differentiation (R = 0.28) within the TME, while showing negative correlations with BRCA stemness (R = - 0.34) and invasion (R = - 0.22). Consequently, TNIP1 is proposed as a potential prognostic marker and therapeutic target for BRCA.

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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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