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髓母细胞瘤中Wnt枢纽基因表达的临床预后意义

Clinical Prognostic Implications of Wnt Hub Genes Expression in Medulloblastoma.

作者信息

Martins-da-Silva Andrea, Baroni Mirella, Salomão Karina Bezerra, das Chagas Pablo Ferreira, Bonfim-Silva Ricardo, Geron Lenisa, Cruzeiro Gustavo Alencastro Veiga, da Silva Wilson Araújo, Corrêa Carolina Alves Pereira, Carlotti Carlos Gilberto, de Paula Queiroz Rosane Gomes, Marie Suely Kazue Nagahashi, Brandalise Silvia Regina, Yunes José Andrés, Scrideli Carlos Alberto, Valera Elvis Terci, Tone Luiz Gonzaga

机构信息

Department of Pediatrics, University Hospital - Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, Brazil.

Department of Genetics, Ribeirão Preto Medical School - University of São Paulo, Ribeirão Preto, Brazil.

出版信息

Cell Mol Neurobiol. 2023 Mar;43(2):813-826. doi: 10.1007/s10571-022-01217-4. Epub 2022 Apr 2.

Abstract

Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.

摘要

髓母细胞瘤是最常见的小儿恶性原发性脑肿瘤,约三分之一的患者因疾病复发而死亡,大多数幸存者患有长期副作用。髓母细胞瘤在临床、基因和表观遗传上具有异质性,至少可分为四个分子亚组:WNT、SHH、3组和4组。我们使用生物信息学方法评估了巴西RNA测序GSE181293数据集与小儿髓母细胞瘤样本微阵列GSE85217数据集队列之间的常见差异表达基因,以便基于蛋白质-蛋白质相互作用(PPI)网络构建、生存和功能分析来识别分子亚组的核心基因。主要发现是从WNT亚组中鉴定出五个作为肿瘤抑制因子的核心基因,其低表达与髓母细胞瘤患者的预后较差有关。此外,与这五个肿瘤抑制因子相关的常见基因参与了肿瘤发生和进展以及发育和分化的重要途径和过程,其中一些基因控制细胞干性和多能性。这些基因尚未在髓母细胞瘤的背景下进行研究,它们是寻找治疗靶点、预后标志物或理解髓母细胞瘤生物学的新的重要研究元素。

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