Soltero-Rivera Maria, Shaw Claire, Arzi Boaz, Lommer Milinda, Weimer Bart C
Department of Surgical and Radiological Sciences, University of California, Davis, CA 95616, USA.
Department of Population Health and Reproduction, 100K Pathogen Genome Project, University of California, Davis, CA 95616, USA.
Pathogens. 2024 Feb 21;13(3):192. doi: 10.3390/pathogens13030192.
Feline chronic gingivostomatitis (FCGS) is a debilitating inflammatory oral mucosal disease with a multifactorial etiology. The clinical diagnosis of FCGS is made based on inspection of severe inflammatory lesions and histological confirmation rather than a molecular diagnostic outcome. This gap limits the ability to provide an early diagnosis. In this report, we seek to provide additional diagnostic tools using genomics to aid in providing clinically relevant information. The use of in-depth diagnostic tools, like transcriptomics of diseased tissues, to diagnose FCGS and stratify patients into predictive treatment response groups would dramatically improve both clinical decisions and patient outcomes. In this study, we addressed the gap in diagnostic options using transcriptomic analysis of caudal oral mucosal swab specimens coupled to detailed medical record linkage of FCGS-affected cats undergoing tooth extractions and in some cases administration of mesenchymal stromal cells (MSCs). To better identify markers of disease and potential response to treatment, the transcriptomes of FCGS-afflicted cats were compared to those of healthy cats and those with chronic periodontitis to clearly establish diagnostic biomarker signal transduction connections. Phosphatidylinositol 3-kinase/Ak strain transforming (PI3K/AKT) and stress-activated protein kinases/Jun N-terminal kinase (SAP/JNK) signaling pathways were significantly differentially regulated in FCGS-afflicted cats. Activation of these pathways also differed in the treatment response groups. In conjunction, the enzymes Caspase 4 (CASP4), matrix metalloproteinase-8 (MMP8), and prostaglandin-endoperoxide synthase 2 (PTGS2) were identified as potential biomarkers for the prediction of treatment response outcomes. The observations in the case study support the use of transcriptomics of FCGS patients to contribute to improved molecular diagnostics for the diagnosis and treatment of FCGS.
猫慢性龈口炎(FCGS)是一种病因多因素的使人衰弱的炎性口腔黏膜疾病。FCGS的临床诊断基于对严重炎性病变的检查和组织学确认,而非分子诊断结果。这一差距限制了早期诊断的能力。在本报告中,我们试图利用基因组学提供额外的诊断工具,以帮助提供临床相关信息。使用深入的诊断工具,如患病组织的转录组学,来诊断FCGS并将患者分层为预测性治疗反应组,将显著改善临床决策和患者预后。在本研究中,我们通过对尾侧口腔黏膜拭子标本进行转录组分析,并结合对接受拔牙且在某些情况下接受间充质基质细胞(MSC)治疗的FCGS患猫的详细病历关联,解决了诊断选择方面的差距。为了更好地识别疾病标志物和对治疗的潜在反应,将FCGS患猫的转录组与健康猫以及患有慢性牙周炎的猫的转录组进行比较,以明确建立诊断生物标志物信号转导联系。磷脂酰肌醇3激酶/阿克曼氏鼠胸腺瘤病毒致癌基因同源物(PI3K/AKT)和应激激活蛋白激酶/应激活化蛋白激酶(SAP/JNK)信号通路在FCGS患猫中存在显著差异调节。这些通路的激活在治疗反应组中也有所不同。此外,半胱天冬酶4(CASP4)、基质金属蛋白酶8(MMP8)和前列腺素内过氧化物合酶2(PTGS2)被确定为预测治疗反应结果的潜在生物标志物。该病例研究中的观察结果支持使用FCGS患者的转录组学来改进FCGS诊断和治疗的分子诊断。