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结直肠癌中基因表达/甲基化和 miRNA 谱的更新；在诊断、预后和靶向治疗中的应用。

Update of gene expression/methylation and MiRNA profiling in colorectal cancer; application in diagnosis, prognosis, and targeted therapy.

机构信息

Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Medical Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

PLoS One. 2022 Mar 25;17(3):e0265527. doi: 10.1371/journal.pone.0265527. eCollection 2022.

DOI:10.1371/journal.pone.0265527
PMID:35333898
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8956198/
Abstract

BACKGROUND

Colorectal cancer is one of the most deadliest malignancies worldwide. Due to the dearth of appropriate biomarkers, the diagnosis of this mortal disease is usually deferred, in its turn, culminating in the failure of prevention. By the same token, proper biomarkers are at play in determining the quality of prognosis. In other words, the survival rate is contingent upon the regulation of such biomarkers.

MATERIALS AND METHODS

The information regarding expression (GSE41258, and GSE31905), methylation (GSE101764), and miRNA (dbDEMC) were downloaded. MEXPRESS and GEPIA confirmed the validated differentially expressed/methylated genes using TCGA data. Taking advantage of the correlation plots and receiver-operating-characteristic (ROC) curves, expression and methylation profiles were compared. The interactions between validated differentially expressed genes and differentially expressed miRNA were recognized and visualized by miRTarBase and Cytoscape, respectively. Then, the protein-protein interaction (PPI) network and hub genes were established via STRING and Cytohubba plugin. Utilizing R packages (DOSE, Enrichplot, and clusterProfiler) and DAVID database, the Functional Enrichment analysis and the detection of KEGG pathways were performed. Ultimately, in order to recognize the prognostic value of found biomarkers, they were evaluated through drawing survival plots for CRC patients.

RESULTS

In this research, we found an expression profile (with 13 novel genes), a methylation profile (with two novel genes), and a miRNA profile with diagnostic value. Concerning diagnosis, the expression profile was evaluated more powerful in comparison with the methylation profile. Furthermore, a prognosis-related expression profile was detected.

CONCLUSION

In addition to diagnostic- and prognostic-applicability, the discerned profiles can assist in targeted therapy and current therapeutic strategies.

摘要

背景

结直肠癌是全球最致命的恶性肿瘤之一。由于缺乏适当的生物标志物，这种致命疾病的诊断通常被推迟，进而导致预防失败。同样，适当的生物标志物在确定预后质量方面起着重要作用。换句话说，存活率取决于这些生物标志物的调节。

材料和方法

下载了表达（GSE41258 和 GSE31905）、甲基化（GSE101764）和 miRNA（dbDEMC）的信息。使用 TCGA 数据，MEXPRESS 和 GEPIA 证实了验证的差异表达/甲基化基因。利用相关图和接收者操作特征（ROC）曲线，比较了表达和甲基化谱。通过 miRTarBase 和 Cytoscape 分别识别和可视化验证的差异表达基因和差异表达 miRNA 之间的相互作用。然后，通过 STRING 和 Cytohubba 插件建立蛋白质-蛋白质相互作用（PPI）网络和枢纽基因。利用 R 包（DOSE、Enrichplot 和 clusterProfiler）和 DAVID 数据库，进行功能富集分析和 KEGG 通路检测。最终，为了识别发现的生物标志物的预后价值，通过为 CRC 患者绘制生存图来评估它们。

结果

在这项研究中，我们发现了一个具有诊断价值的表达谱（有 13 个新基因）、一个甲基化谱（有两个新基因）和一个 miRNA 谱。在诊断方面，与甲基化谱相比，表达谱的评估更为强大。此外，还检测到了与预后相关的表达谱。

结论

除了诊断和预后适用性外，所发现的谱还可以帮助进行靶向治疗和当前的治疗策略。

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