AGO2 蛋白:miRNA 通路中的关键酶,作为肾上腺皮质癌的新型生物标志物。
AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma.
发表日期:2024 Oct 01
作者:
Anila Hashmi, Alexander Papachristos, Stan B Sidhu, Gyorgy Hutvagner
来源:
ENDOCRINE-RELATED CANCER
摘要:
肾上腺皮质癌(ACC)是一种罕见的侵袭性恶性肿瘤,其特点是诊断困难、复发率高和预后不良。本研究探讨了 microRNA (miRNA) 处理基因在 ACC 中的作用,及其作为诊断和预后生物标志物的潜在作用。我们利用癌症基因组图谱 (TCGA) 和基因型组织表达 (GTEx) 项目的 mRNA-Seq 数据分析了 miRNA 机械组件(DROSHA、DGCR8、XPO5、RAN、DICER、TARBP2 和 AGO2)的 mRNA 表达水平。此外,还对科林医学研究所肿瘤库的组织样本中的蛋白质水平进行了定量。我们的结果表明,在所有 miRNA 加工组件中,与正常肾上腺皮质 (NAC) 和良性肾上腺腺瘤 (AA) 相比,AGO2 在 ACC 中表现出显着的过表达 (p < 0.001)。 Kaplan-Meier 生存分析表明,较高的 AGO2 表达与 ACC 患者的总生存率显着较差相关(HR 7.07,p < 0.001)。在 TCGA 的 32 种癌症类型中,AGO2 在 ACC 中的预后意义最为突出。这项研究首次报道了 AGO2 作为 ACC 诊断和预后生物标志物的潜力,强调了其在 ACC 发病机制中的重要性以及作为非侵入性液体活检生物标志物的潜在应用。
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy characterised by diagnostic challenges, high recurrence rates, and poor prognosis. This study explored the role microRNA (miRNA) processing genes in ACC, and their potential role as diagnostic and prognostic biomarkers. We analysed the mRNA expression levels of miRNA machinery components (DROSHA, DGCR8, XPO5, RAN, DICER, TARBP2 and AGO2) utilising mRNA-Seq data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) projects. Additionally, protein levels were quantified in tissue samples from the Kolling Institute of Medical Research's tumour bank. Our results demonstrated that among all miRNA processing components, AGO2 exhibited significant overexpression in ACC compared to the normal adrenal cortex (NAC) and benign adrenal adenoma (AA) (p < 0.001). Kaplan-Meier survival analysis indicated that higher AGO2 expression correlated with significantly worse overall survival in ACC patients (HR 7.07, p < 0.001). Among 32 cancer types in TCGA, the prognostic significance of AGO2 was most prominent in ACC. This study is the first to report AGO2's potential as a diagnostic and prognostic biomarker in ACC, emphasising its significance in ACC pathogenesis and potential application as a non-invasive liquid biopsy biomarker.