ITGB3 是一种新型预后生物标记物,与透明细胞肾细胞癌的甲基化异常和肿瘤免疫相关。

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2024-08-12 DOI:10.2174/0113862073311689240730112355
Hao-Yun Luo, Jun-Ming Feng, Jun Luo, Tian Tian
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引用次数: 0

摘要

背景:尽管晚期肾癌的治疗仍面临挑战,但目前的证据表明透明细胞肾癌(ccRCC)是最常见的肾癌形式。Integrin subunit beta 3(ITGB3)最近被认为是肿瘤发生过程中的一个关键角色,这促使我们研究它在ccRCC中的作用。本研究旨在阐明ITGB3下调的机制,并评估其临床意义,尤其是对ccRCC内免疫环境的影响:我们首先利用TCGA和GEO数据集的数据进行分析,探讨ITGB3在ccRCC组织中的表达。随后,我们评估了 ITGB3 表达水平与患者预后和病理分期之间的关联。我们进行了通路和功能富集分析,以评估 ITGB3 与免疫和甲基化相关通路之间的相关性。此外,我们还研究了ITGB3转录表达与DNA高甲基化之间的关系。通过对选定的 ITGB3 相关 DNA 甲基化探针进行基于 LASSO 的分析,我们建立了一个预后风险模型。免疫组化(IHC)分析与TIMER和ssGSEA结果一起用于研究ITGB3的表达及其与免疫细胞浸润的关系:我们的分析表明,与ITGB家族的其他成员相比,ITGB3 mRNA在ccRCC组织中的表达明显下调,这在TCGA和GEO数据集中是一致的。ITGB3的高表达与ccRCC患者预后的改善和病理分期的降低相关。通路和功能富集分析表明,ITGB3与免疫和甲基化相关通路呈正相关,而ITGB3转录表达与DNA高甲基化呈负相关。已建立的预后风险模型发现,高风险组的生存概率低于低风险组。免疫组化定量分析显示,CD4+和CD8+免疫细胞浸润与ITGB3表达呈正相关:总之,我们的研究提供了令人信服的证据,支持 ITGB3 在 ccRCC 免疫中的重要作用。ITGB3的下调及其与较好预后和免疫激活的相关性表明,ITGB3有可能成为这一患者群体的治疗靶点和预后标志物。
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ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma.

Background: Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.

Methods: We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration.

Results: Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression.

Conclusion: Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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