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作为肝细胞癌预后标志物的[具体基因]过表达:基于TCGA数据的分析

Overexpression of as a prognostic marker in hepatocellular carcinoma: A TCGA data-based analysis.

作者信息

Yang Pan, Liu Huaifeng, Li Yan, Gao Qunwei, Chen Xin, Chang Junyan, Li Yangyang, Chen Shuran, Dong Rui, Wu Huazhang, Liu Changqing, Liu Gaofeng

机构信息

School of Life Science, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China.

Department of Gynecologic Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.

出版信息

Front Genet. 2022 Oct 10;13:959832. doi: 10.3389/fgene.2022.959832. eCollection 2022.

Abstract

Transcription elongation factor 1 () is a nuclear protein consisted of multiple protein structural domains that plays an important role in regulating the transcription, extension, and splicing regulation of RNA polymerase II. However, the prognostic and immunological role of 1 in human cancer remains unknown. In this study, we analyzed the expression of gene in hepatocellular carcinoma (HCC) patients, its clinical significance, and its possible prognostic value by bioinformatics. RNA sequencing data and clinicopathological characteristics of patients with HCC were collected from TCGA and CCLE databases. The Wilcoxon rank-sum test was used to analyze the expression of in HCC tissues and normal tissues. The protein levels of between normal and liver cancer tissues were analyzed by the Human Protein Atlas Database (HPA) (www.proteinatlas.org). Validation was performed using the Gene Expression Omnibus (GEO) dataset of 167 samples. The expression of in HCC cells were verified by qRT-PCR, and CCK-8, scratch assay and Transwell assay were performed to detect cell proliferation, migration and invasion ability. According to the median value of expression, patients were divided into high and low subgroups. Logistic regression, GSEA enrichment, TME, and single-sample set gene enrichment analysis (ssGSEA) were performed to explore the effects of on liver cancer biological function and immune infiltrates. co-expression networks were studied through the CCLE database and the LinkedOmics database to analyze genes that interact with . The expression levels of in HCC patient tissues were significantly higher than in normal tissues. Survival analysis showed that high levels of expression were significantly associated with low survival rates in HCC patients. Multifactorial analysis showed that high expression was an independent risk factor affecting tumor prognosis. This result was also verified in the GEO database. Cellular experiments demonstrated that cell proliferation, migration and invasion were inhibited after silencing of gene expression. Co-expression analysis revealed that and expression were positively correlated with . GSEA showed that in samples with high expression, relevant signaling pathways associated with cell cycle, apoptosis, pathways in cancer and enriched in known tumors included Wnt signaling pathway, Vegf signaling pathway, Notch signaling pathway, MAPK signaling pathway and MTOR pathways. The expression of was positively correlated with tumor immune infiltrating cells (T helper two cells, T helper cells). gene is highly expressed in hepatocellular carcinoma tissues, which is associated with the poor prognosis of liver cancer, and may be one of the markers for the diagnosis and screening of liver cancer and the prediction of prognosis effect. At the same time, may also become a new target for tumor immunotherapy.

摘要

转录延伸因子1()是一种由多个蛋白质结构域组成的核蛋白,在调节RNA聚合酶II的转录、延伸和剪接调控中发挥重要作用。然而,1在人类癌症中的预后和免疫作用仍不清楚。在本研究中,我们通过生物信息学分析了1基因在肝细胞癌(HCC)患者中的表达、其临床意义及其可能的预后价值。从TCGA和CCLE数据库收集HCC患者的RNA测序数据和临床病理特征。采用Wilcoxon秩和检验分析1在HCC组织和正常组织中的表达。通过人类蛋白质图谱数据库(HPA)(www.proteinatlas.org)分析正常组织和肝癌组织之间1的蛋白质水平。使用167个样本的基因表达综合数据库(GEO)数据集进行验证。通过qRT-PCR验证1在HCC细胞中的表达,并进行CCK-8、划痕试验和Transwell试验以检测细胞增殖、迁移和侵袭能力。根据1表达的中位数,将患者分为高表达和低表达亚组。进行逻辑回归、基因集富集分析(GSEA)、肿瘤微环境(TME)和单样本基因集富集分析(ssGSEA)以探讨1对肝癌生物学功能和免疫浸润的影响。通过CCLE数据库和LinkedOmics数据库研究1共表达网络,以分析与1相互作用的基因。1在HCC患者组织中的表达水平显著高于正常组织。生存分析表明,1高表达与HCC患者的低生存率显著相关。多因素分析表明,1高表达是影响肿瘤预后的独立危险因素。该结果也在GEO数据库中得到验证。细胞实验表明,沉默1基因表达后,细胞增殖、迁移和侵袭受到抑制。共表达分析显示,1和的表达与1呈正相关。GSEA表明,在1高表达的样本中,与细胞周期、凋亡、癌症相关信号通路以及已知肿瘤中富集的信号通路包括Wnt信号通路、Vegf信号通路、Notch信号通路、MAPK信号通路和MTOR通路。1的表达与肿瘤免疫浸润细胞(辅助性T细胞2、辅助性T细胞)呈正相关。1基因在肝细胞癌组织中高表达,这与肝癌的不良预后相关,可能是肝癌诊断和筛查以及预后效果预测的标志物之一。同时,1也可能成为肿瘤免疫治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bd5/9589486/7e43dafbb2e4/fgene-13-959832-g001.jpg

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