Esmaeili Motlagh Parisa, Ghafouri-Fard Soudeh, Eslami Solat, Sharifi Guive, Taheri Mohammad
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
Discov Oncol. 2024 Sep 27;15(1):486. doi: 10.1007/s12672-024-01338-w.
Non-functioning pituitary adenomas (NFPAs) are a group of these neoplasms originated from the adenohypophyse and do not show evidence of hormonal oversecretion. However, different genes and lncRNAs have been found to be dysregulated in these samples.
In this study, in order to identify novel biomarkers, a set of regulatory lncRNAs for the two important hub genes, i.e. STAT3 and EGFR were selected and subjected to experimental investigation. These lncRNAs were EGFR-AS1 for the EGFR gene, and LINC00240, FALEC and SNHG12 for the STAT3 gene.
All studied genes were down-regulated in NFPA samples compared with normal tissues adjacent to the tumors (NTATs), except for FALEC whose expression was not different between these two sets of samples. EGFR was the most significantly down-regulated gene in NFPAs (Expression ratio (95% CI) = 0.009 (0.002-0.04), P value < 0.0001). ROC curve analyses proposed that the expression levels of SNHG12, EGFR, EGFR-AS1 and LINC00240 can be used to distinguish NFPAs from NTATs with AUC values of 0.88, 0.83, 0.7 and 0.66, respectively. Spearman's correlation analyses showed significant correlations between FALEC and EGFR-AS1 in both types of tissues, and between FALEC and EGFR in NFPAs. Moreover, expression of LINC00240 was correlated with EGFR-AS1, FALEC and SNHG12 in NFPAs.
Taken together, EGFR and STAT3-related lncRNAs may be involved in the pathogenesis of NFPA.
无功能垂体腺瘤(NFPAs)是一组起源于腺垂体且无激素分泌过多证据的肿瘤。然而,已发现这些样本中不同的基因和长链非编码RNA(lncRNAs)表达失调。
在本研究中,为了鉴定新的生物标志物,选择了一组针对两个重要枢纽基因即信号转导和转录激活因子3(STAT3)和表皮生长因子受体(EGFR)的调控lncRNAs,并进行实验研究。这些lncRNAs中,针对EGFR基因的是EGFR-AS1,针对STAT3基因的是LINC00240、FALEC和SNHG12。
与肿瘤旁正常组织(NTATs)相比,所有研究基因在NFPA样本中均下调,但FALEC在这两组样本中的表达无差异。EGFR是NFPA中下调最显著的基因(表达比值(95%置信区间)=0.009(0.002 - 0.04),P值<0.0001)。ROC曲线分析表明,SNHG12、EGFR、EGFR-AS1和LINC00240的表达水平可用于区分NFPA和NTATs,其曲线下面积(AUC)值分别为0.88、0.83、0.7和0.66。Spearman相关性分析显示,在两种组织类型中FALEC与EGFR-AS1之间以及在NFPA中FALEC与EGFR之间均存在显著相关性。此外,在NFPA中LINC00240的表达与EGFR-AS1、FALEC和SNHG12相关。
综上所述,EGFR和STAT3相关的lncRNAs可能参与了NFPA的发病机制。