Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran.
Department of Applied Mathematics, Faculty of Mathematical Sciences, Tarbiat Modares University, Tehran, Iran.
Iran Biomed J. 2023 Sep 1;27(5):294-306. doi: 10.61186/ibj.27.5.294. Epub 2023 Mar 27.
Adenoid cystic carcinoma is a slow-growing malignancy that most often occurs in the salivary glands. Currently, no FDA-approved therapeutic target or diagnostic biomarker has been identified for this cancer. The aim of this study was to find new therapeutic and diagnostic targets using bioinformatics methods.
We extracted the gene expression information from two GEO datasets (including GSE59701 and GSE88804). Different expression genes between adenoid cystic carcinoma (ACC) and normal samples were extracted using R software. The biochemical pathways involved in ACC were obtained by using the Enrichr database. PPI network was drawn by STRING, and important genes were extracted by Cytoscape. Real-time PCR and immunohistochemistry were used for biomarker verification.
After analyzing the PPI network, 20 hub genes were introduced to have potential as diagnostic and therapeutic targets. Among these genes, PLCG1 was presented as new biomarker in ACC. Furthermore, by studying the function of the hub genes in the enriched biochemical pathways, we found that insulin-like growth factor type 1 receptor and PPARG pathways most likely play a critical role in tumorigenesis and drug resistance in ACC and have a high potential for selection as therapeutic targets in future studies.
In this study, we achieved the recognition of the pathways involving in ACC pathogenesis and also found potential targets for treatment and diagnosis of ACC. Further experimental studies are required to confirm the results of this study.
腺样囊性癌是一种生长缓慢的恶性肿瘤,最常发生在唾液腺。目前,尚未确定该癌症的 FDA 批准的治疗靶点或诊断生物标志物。本研究旨在通过生物信息学方法寻找新的治疗和诊断靶点。
我们从两个 GEO 数据集(包括 GSE59701 和 GSE88804)中提取了基因表达信息。使用 R 软件提取腺样囊性癌(ACC)和正常样本之间差异表达的基因。使用 Enrichr 数据库获得与 ACC 相关的生化途径。通过 STRING 绘制 PPI 网络,并通过 Cytoscape 提取重要基因。使用实时 PCR 和免疫组织化学法进行生物标志物验证。
通过分析 PPI 网络,引入了 20 个关键基因作为诊断和治疗靶点的潜在候选物。在这些基因中,PLCG1 被认为是 ACC 的新生物标志物。此外,通过研究这些关键基因在富集的生化途径中的功能,我们发现胰岛素样生长因子 1 型受体和 PPARG 途径极有可能在 ACC 的肿瘤发生和耐药性中发挥关键作用,并且很有潜力作为未来研究中的治疗靶点。
在本研究中,我们实现了对涉及 ACC 发病机制的途径的识别,并且发现了 ACC 治疗和诊断的潜在靶点。需要进一步的实验研究来验证本研究的结果。