Giantin Mery, Montanucci Ludovica, Lopparelli Rosa Maria, Tolosi Roberta, Dentini Alfredo, Grieco Valeria, Stefanello Damiano, Sabattini Silvia, Marconato Laura, Pauletto Marianna, Dacasto Mauro
Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università 16, I-35020 Legnaro, PD, Italy.
Department of Neurology, Mc Govern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 44106, USA.
Genes (Basel). 2025 Mar 14;16(3):340. doi: 10.3390/genes16030340.
BACKGROUND/OBJECTIVES: Mast cell tumors (MCTs) are the second most common malignant neoplasms in dogs. Histopathological grading and clinical staging are the main tools for estimating biological behavior and disease extent; thus, both are essential for therapeutic decision-making and prognostication. However, the biological behavior of MCTs in dogs is variable, and it sometimes deviates from expectations. In a previous study, we identified 12 transcripts whose expression profile allowed a clear distinction between Kiupel low-grade and high-grade cutaneous MCTs (cMCTs) and was associated with prognosis. Building on these findings, this study evaluated the predictive potential of these transcripts' expression profiles in classifying cMCTs into low-grade and high-grade.
A logistic regression classifier based on the expression profiles of the identified transcripts and able to classify cMCTs as low- or high-grade was developed and subsequently tested on a novel dataset of 50 cMCTs whose expression profiles have been determined in this study through qPCR.
The developed logistic regression classifier reaches an accuracy of 67% and an area under the receiver operating characteristic curve (AUC) of 0.76. Interestingly, the molecular classification clearly identifies stage-IV disease (90% true positive rate).
qPCR analysis of these biomarkers combined with the machine learning-based classifier might serve as a tool to support cMCT clinical management at diagnosis.
背景/目的:肥大细胞瘤(MCTs)是犬类中第二常见的恶性肿瘤。组织病理学分级和临床分期是评估生物学行为和疾病范围的主要工具;因此,两者对于治疗决策和预后判断都至关重要。然而,犬类MCTs的生物学行为具有变异性,有时会与预期不符。在先前的一项研究中,我们鉴定出12种转录本,其表达谱能够清晰区分Kiupel低级别和高级别皮肤MCTs(cMCTs),并与预后相关。基于这些发现,本研究评估了这些转录本表达谱在将cMCTs分为低级别和高级别方面的预测潜力。
开发了一种基于已鉴定转录本表达谱的逻辑回归分类器,能够将cMCTs分类为低级别或高级别,随后在一个新的包含50个cMCTs的数据集上进行测试,该数据集的表达谱已在本研究中通过定量聚合酶链反应(qPCR)确定。
所开发的逻辑回归分类器的准确率达到67%,受试者工作特征曲线(AUC)下面积为0.76。有趣的是,分子分类能够明确识别IV期疾病(真阳性率为90%)。
对这些生物标志物进行qPCR分析并结合基于机器学习的分类器,可能作为一种工具来支持cMCT诊断时的临床管理。