Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece.
Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, Mezourlo, 41500 Larissa, Greece.
Biomolecules. 2024 Oct 24;14(11):1352. doi: 10.3390/biom14111352.
Breast cancer ranks first in incidence and second in deaths worldwide, presenting alarmingly rising mortality rates. Imaging methodologies and/or invasive biopsies are routinely used for screening and detection, although not always with high sensitivity/specificity. MicroRNAs (miRNAs) could serve as diagnostic and prognostic biomarkers for breast cancer. We have designed a computational approach combining transcriptome profiling, survival analyses, and diagnostic power calculations from 1165 patients with breast invasive carcinoma from The Cancer Genome Atlas (TCGA-BRCA). Our strategy yielded two separate miRNA signatures consisting of four up-regulated and five down-regulated miRNAs in breast tumors, with cumulative diagnostic strength of AUC 0.93 and 0.92, respectively. We provide direct evidence regarding the breast cancer-specific expression of both signatures through a multicancer comparison of >7000 biopsies representing 19 solid cancer types, challenging their diagnostic potency beyond any of the current diagnostic methods. Our signatures are functionally implicated in cancer-related processes with statistically significant effects on overall survival and lymph-node invasion in breast cancer patients, which underlie their strong prognostic implication. Collectively, we propose two novel miRNA signatures with significantly elevated diagnostic and prognostic power as a functionally resolved tool for binary and accurate detection of breast cancer and other tumors of the female reproductive system.
乳腺癌在全球的发病率位居第一，死亡率位居第二，呈现出惊人的上升趋势。影像学方法和/或侵入性活检通常用于筛查和检测，尽管其敏感性/特异性并不总是很高。microRNAs（miRNAs）可作为乳腺癌的诊断和预后生物标志物。我们设计了一种计算方法，结合了来自癌症基因组图谱（TCGA-BRCA）的 1165 例乳腺浸润性癌患者的转录组分析、生存分析和诊断能力计算。我们的策略产生了两个独立的 miRNA 特征，包括乳腺肿瘤中四个上调和五个下调的 miRNA，累积诊断 AUC 分别为 0.93 和 0.92。我们通过对 >7000 个活检的多癌症比较提供了这两个特征的乳腺癌特异性表达的直接证据，代表了 19 种实体癌类型，这表明它们的诊断效力超过了任何当前的诊断方法。我们的特征在癌症相关过程中具有功能意义，对乳腺癌患者的总生存和淋巴结浸润具有统计学意义的影响，这是它们强烈预后意义的基础。总之，我们提出了两个具有显著提高的诊断和预后能力的新型 miRNA 特征，作为一种功能明确的工具，可用于二元和准确检测乳腺癌和女性生殖系统的其他肿瘤。
