Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Indian J Med Res. 2024 Jul;160(1):118-127. doi: 10.25259/ijmr_2567_22.
Background & objectives In gastrointestinal stromal tumour (GIST), not only genetic abnormalities are responsible for adverse clinical events, but epigenetic modifications also play a crucial role. MicroRNA (miRNA) dysregulation plays a significant role in carcinogenesis as miRNAs serve as natural silencer for their targets. Our study aimed to explore the miRNAs expression and its association with molecular and histopathological characteristics of GIST. Methods Fifty GIST samples, including 45 formalin fixed paraffin embedded (FFPE) and fresh tissues were included. Peripheral non-tumour tissues were used as controls. All the cases were confirmed using immunohistochemistry. RNA was extracted using miRNA-specific kit, and the expression was performed using RT-qPCR. The data were evaluated using AriaMx software version 1.5 (Agilent, US). MiRNAs expression was analyzed by using the relative quantification method (ΔΔCT). Results miR-221, miR-222, miR-494 and miR-34a showed significant down-regulation in tumours relative to non-tumour tissues. The expression levels of these miRNAs were significantly down-regulated in c-KIT (proto-oncogene encoding the tyrosine kinase transmembrane receptor)-positive tumours compared to c-KIT-negative. Further analysis revealed that reduced expression was associated with spindle subtypes and gastric localization. However, there was no significant correlation with other histological features. Additionally, miR-221/222, and miR-494 were down-regulated in most of the KIT exon 11 mutant subtypes, while miRNA-34a was associated with platelet derived growth factor receptor alpha (PDGFRA) mutations. Interpretation & conclusions The present study showed that the down-regulation of these miRNAs may help better molecular classification and characterization of GISTs. Our results offer new insight into the association between miRNAs and histological features, enabling a more thorough understanding of GISTs at the molecular level.
在胃肠道间质瘤（GIST）中，不仅遗传异常导致不良临床事件，而且表观遗传修饰也起着至关重要的作用。微小 RNA（miRNA）失调在致癌作用中起重要作用，因为 miRNA 作为其靶标的天然沉默子。我们的研究旨在探索 GIST 中 miRNA 的表达及其与分子和组织病理学特征的关系。
本研究纳入了 50 例 GIST 样本，包括 45 例福尔马林固定石蜡包埋（FFPE）和新鲜组织，以及外周非肿瘤组织作为对照。所有病例均采用免疫组织化学法证实。使用 miRNA 特异性试剂盒提取 RNA，并采用 RT-qPCR 进行表达分析。使用 AriaMx 软件版本 1.5（Agilent，美国）评估数据。miRNA 表达采用相对定量法（ΔΔCT）进行分析。
miR-221、miR-222、miR-494 和 miR-34a 在肿瘤组织中的表达相对非肿瘤组织明显下调。与 c-KIT 阴性肿瘤相比，c-KIT（编码酪氨酸激酶跨膜受体的原癌基因）阳性肿瘤中这些 miRNA 的表达水平显著下调。进一步分析显示，表达降低与梭形亚型和胃定位有关。然而，与其他组织学特征无显著相关性。此外，miR-221/222 和 miR-494 在大多数 KIT 外显子 11 突变亚型中下调，而 miR-34a 与血小板衍生生长因子受体 alpha（PDGFRA）突变有关。
本研究表明这些 miRNA 的下调可能有助于更好地对 GIST 进行分子分类和特征描述。我们的结果提供了 miRNA 与组织学特征之间关系的新见解，使我们能够在分子水平上更全面地了解 GIST。
