PRR13 expression as a prognostic biomarker in breast cancer: correlations with immune infiltration and clinical outcomes.

IF 3.9 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in Molecular Biosciences Pub Date : 2025-03-03 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1518031
Mingjing Meng, Jiani Wang, Jiumei Yang, Yangming Zhang, Xusheng Tu, Pan Hu
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Abstract

Introduction: Breast cancer continues to be a primary cause of cancer-related mortality among women globally. Identifying novel biomarkers is essential for enhancing patient prognosis and informing therapeutic decisions. The PRR13 gene, associated with taxol resistance and the progression of various cancers, remains under-characterized in breast cancer. This study aimed to investigate the role of PRR13 in breast cancer and its potential as a prognostic biomarker.

Methods: We performed a comparative analysis of PRR13 gene expression utilizing the TCGA database against non-cancerous tissues and employed STRING to evaluate PRR13's protein-protein interactions and associated pathways. Additionally, we investigated the relationship between PRR13 mRNA expression and immune cell infiltration in breast cancer (BRCA) using two methodologies. Furthermore, a retrospective analysis of 160 patients was conducted, wherein clinical data were collected and PRR13 expression was evaluated through immunohistochemistry and qRT-PCR to determine its association with clinicopathological features and patient survival.

Results: Analysis of the TCGA database revealed significant upregulation of PRR13 expression across 12 different cancer types, including breast cancer. High PRR13 expression was positively correlated with various immune cells, including NK cells, eosinophils, Th17 cells, and mast cells, whereas a negative correlation was observed with B cells, macrophages, and other immune subsets. Enrichment analysis of PRR13 and its 50 interacting proteins revealed significant associations with biological processes such as cell adhesion and migration, and pathways including ECMreceptor interaction and PI3K-Akt signaling. Single-cell analysis demonstrated associations between PRR13 and pathways pertinent to inflammation and apoptosis. Validation studies confirmed elevated PRR13 expression in tumor tissue compared to adjacent non-cancerous tissue. Immunohistochemistry demonstrated high PRR13 expression in 55.6% of cancer cases, particularly associated with advanced clinical stage and lymph node metastasis. Moreover, high PRR13 expression significantly correlated with shorter overall survival and served as an independent prognostic factor. Subgroup analysis underscored the prognostic significance of PRR13 in aggressive tumor subtypes, with particularly strong associations observed in T3, N1-3, and moderately to poorly differentiated tumors.

Discussion: In conclusion, PRR13 expression is upregulated in breast cancer tissues and may serve as a valuable prognostic indicator for breast cancer patients, potentially impacting patient survival and therapeutic strategies.

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PRR13表达作为乳腺癌预后生物标志物:与免疫浸润和临床结果的相关性
导读:乳腺癌仍然是全球妇女癌症相关死亡的主要原因。识别新的生物标志物对于改善患者预后和告知治疗决策至关重要。PRR13基因与紫杉醇耐药性和各种癌症的进展相关,但在乳腺癌中仍未被充分描述。本研究旨在探讨PRR13在乳腺癌中的作用及其作为预后生物标志物的潜力。方法:利用TCGA数据库对非癌组织的PRR13基因表达进行比较分析,并利用STRING评估PRR13蛋白-蛋白相互作用及其相关途径。此外,我们使用两种方法研究了乳腺癌(BRCA)中PRR13 mRNA表达与免疫细胞浸润之间的关系。并对160例患者进行回顾性分析,收集临床资料,通过免疫组织化学和qRT-PCR检测PRR13表达,确定其与临床病理特征及患者生存的关系。结果:TCGA数据库的分析显示,PRR13在包括乳腺癌在内的12种不同癌症类型中表达显著上调。PRR13高表达与NK细胞、嗜酸性粒细胞、Th17细胞和肥大细胞等多种免疫细胞呈正相关,而与B细胞、巨噬细胞等免疫亚群呈负相关。PRR13及其50个相互作用蛋白的富集分析显示,PRR13与细胞粘附和迁移等生物学过程以及包括ecm受体相互作用和PI3K-Akt信号传导在内的途径存在显著关联。单细胞分析表明,PRR13与炎症和凋亡相关通路之间存在关联。验证研究证实,与邻近非癌组织相比,PRR13在肿瘤组织中的表达升高。免疫组织化学显示55.6%的癌症病例中PRR13高表达,特别是与晚期临床阶段和淋巴结转移相关。此外,高PRR13表达与较短的总生存期显著相关,并可作为独立的预后因素。亚组分析强调了PRR13在侵袭性肿瘤亚型中的预后意义,在T3、N1-3和中分化至低分化肿瘤中观察到特别强的相关性。综上所述,PRR13在乳腺癌组织中表达上调,可能作为乳腺癌患者有价值的预后指标,可能影响患者的生存和治疗策略。
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来源期刊
Frontiers in Molecular Biosciences
Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
7.20
自引率
4.00%
发文量
1361
审稿时长
14 weeks
期刊介绍: Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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