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GINS1的上调凸显了其在三种不同人类癌症亚型中良好的生存诊断和预后潜力。

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer.

作者信息

Ahmad M, Hameed Y, Khan M, Usman M, Rehman A, Abid U, Asif R, Ahmed H, Hussain M S, Rehman J U, Asif H M, Arshad R, Atif M, Hadi A, Sarfraz U, Khurshid U

机构信息

The Islamia University of Bahawalpur, Department of Biochemistry and Biotechnology, Bahawalpur, Pakistan.

The Islamia University of Bahawalpur, Department of Pharmacy, Bahawalpur, Pakistan.

出版信息

Braz J Biol. 2021 Nov 26;84:e250575. doi: 10.1590/1519-6984.250575. eCollection 2021.

Abstract

Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

摘要

癌症是一种致命的恶性肿瘤,其在全球范围内的患病率不断上升,这就需要发现更敏感、可靠的分子生物标志物。使用一系列多层次的计算机分析方法来研究GINS1在不同人类癌症中的表达水平及其预后价值,可能有助于将其确立为不同癌症亚型潜在的共享诊断和预后生物标志物。使用UALCAN和人类蛋白质图谱(HPA)分析GINS1 mRNA、蛋白质表达和启动子甲基化,同时通过GENT2进一步验证mRNA表达。通过KM plotter评估GINS1的潜在预后价值。然后,利用cBioPortal检查与GINS1相关的基因突变和拷贝数变异(CNV),同时使用DAVID进行通路富集分析。此外,使用TIMER、CDT和Cytoscape进行GINS1表达与CD8 + T免疫细胞之间的相关性分析以及基因-药物相互作用网络的构建。发现GINS1在人类癌症的单一亚型中下调,而在其他23种不同亚型中通常上调。GINS1的上调与肝细胞肝癌(LIHC)、肺腺癌(LUAD)和肾透明细胞癌(KIRC)的总体生存率差显著相关。在不同临床病理特征的LIHC、LUAD和KIRC患者中也发现GINS1上调。通路富集分析显示GINS1参与两条不同的通路,同时还记录了GINS1表达与其启动子甲基化水平、CD8 + T免疫细胞水平和CNV之间的一些有趣相关性。此外,我们还预测了一些可通过调节GINS1表达用于治疗LIHC、LUAD和KIRC的药物。本研究中GINS1的表达谱表明它是LIHC、LUAD和KIRC一种新型的共享诊断和预后生物标志物。

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