Elshafie Nelly O, Gribskov Michael, Lichti Nathanael I, Sayedahmed Ekramy E, Childress Michael O, Dos Santos Andrea P
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, United States.
Department of Biological Sciences, Purdue University, West Lafayette, IN, United States.
Front Oncol. 2023 Aug 30;13:1238613. doi: 10.3389/fonc.2023.1238613. eCollection 2023.
Lymphoma is a common canine cancer with translational relevance to human disease. Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype, contributing to almost fifty percent of clinically recognized lymphoma cases. Identifying new biomarkers capable of early diagnosis and monitoring DLBCL is crucial for enhancing remission rates. This research seeks to advance our knowledge of the molecular biology of DLBCL by analyzing the expression of microRNAs, which regulate gene expression by negatively impacting gene expression via targeted RNA degradation or translational repression. The stability and accessibility of microRNAs make them appropriate biomarkers for the diagnosis, prognosis, and monitoring of diseases.
We extracted and sequenced microRNAs from ten fresh-frozen lymph node tissue samples (six DLBCL and four non-neoplastic).
Small RNA sequencing data analysis revealed 35 differently expressed miRNAs (DEMs) compared to controls. RT-qPCR confirmed that 23/35 DEMs in DLBCL were significantly upregulated (n = 14) or downregulated (n = 9). Statistical significance was determined by comparing each miRNA's average expression fold-change (2-Cq) between the DLCBL and healthy groups by applying the unpaired parametric Welch's 2-sample t-test and false discovery rate (FDR). The predicted target genes of the DEMs were mainly enriched in the PI3K-Akt-MAPK pathway.
Our data point to the potential value of miRNA signatures as diagnostic biomarkers and serve as a guideline for subsequent experimental studies to determine the targets and functions of these altered miRNAs in canine DLBCL.
淋巴瘤是一种常见的犬类癌症，与人类疾病具有转化相关性。弥漫性大B细胞淋巴瘤（DLBCL）是最常见的亚型，占临床确诊淋巴瘤病例的近50%。识别能够早期诊断和监测DLBCL的新生物标志物对于提高缓解率至关重要。本研究旨在通过分析微小RNA的表达来推进我们对DLBCL分子生物学的认识，微小RNA通过靶向RNA降解或翻译抑制对基因表达产生负面影响从而调节基因表达。微小RNA的稳定性和可及性使其成为疾病诊断、预后和监测的合适生物标志物。
我们从10个新鲜冷冻的淋巴结组织样本（6个DLBCL样本和4个非肿瘤样本）中提取并测序了微小RNA。
与对照组相比，小RNA测序数据分析揭示了35个差异表达的微小RNA（DEM）。RT-qPCR证实，DLBCL中的23/35个DEM显著上调（n = 14）或下调（n = 9）。通过应用未配对参数韦尔奇两样本t检验和错误发现率（FDR）比较DLCBL组和健康组之间每个微小RNA的平均表达倍数变化（2-Cq）来确定统计学意义。DEM的预测靶基因主要富集在PI3K-Akt-MAPK通路中。
我们的数据表明微小RNA特征作为诊断生物标志物的潜在价值，并为后续实验研究提供指导，以确定这些改变的微小RNA在犬类DLBCL中的靶标和功能。
