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胶质细胞成熟因子-γ 在多种癌症中的生物信息学和生存分析。

Bioinformatics and survival analysis of glia maturation factor-γ in pan-cancers.

机构信息

Central Laboratory, the Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China.

Center for Reproductive Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, China.

出版信息

BMC Cancer. 2021 Apr 17;21(1):423. doi: 10.1186/s12885-021-08163-2.

Abstract

BACKGROUND

Glia maturation factor-γ (GMFG) is reported to inhibit the actin nucleation through binding to the actin-related protein-2/3 complex (Arp2/3). Considering the main function of GMFG in actin remodeling, which is vital for immune response, angiogenesis, cell division and motility, GMFG is supposed to have important roles in tumor development, while up to now, only two studies described the role of GMFG in cancers. By investigating the clinical values of GMFG using The Cancer Genome Atlas (TCGA) data and the functional mechanisms of GMFG through analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, this study was aimed to better understand the impact of GMFG in pan-cancers and to draw more attentions for the future research of GMFG.

METHODS

RNA-seq and clinical data of cancer patients were collected from TCGA and analyzed by the Kaplan-Meier methods. GO and KEGG analyses were conducted using the online tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID).

RESULTS

Compared to the corresponding normal samples, GMFG was significantly upregulated in glioblastoma (GBM), kidney clear cell carcinoma (KIRC), lower grade glioma (LGG), acute myeloid leukemia (LAML), and pancreatic cancer (PAAD), testicular cancer (TGCT), but was downregulated in kidney chromophobe (KICH), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) (P < 0.05 for all). High expression of GMFG predicted worse OS in GBM (HR = 1.5, P = 0.017), LGG (HR = 2.2, P < 0.001), LUSC (HR = 1.4, P = 0.022) and ocular melanomas (UVM) (HR = 7, P < 0.001), as well as worse DFS in LGG (HR = 1.8, P < 0.001) and prostate cancer (PRAD) (HR = 1.9, P = 0.004). In contrast, high expression of GMFG was associated with better OS in skin cutaneous melanoma (SKCM) (HR = 0.59, P < 0.001) and thymoma (THYM) (HR = 0.098, P = 0.031), as well as better DFS in bile duct cancer (CHOL) (HR = 0.2, P = 0.003). GMFG was mainly involved in the immune response, protein binding and cytokine-cytokine receptor interaction pathways, and was positively associated with multiple immunomodulators in most cancers.

CONCLUSION

Our study preliminarily identified that GMFG may cause different survivals for different cancers through modulating tumor progression, immune response status and tissue-specific tumor microenvironment (TME).

摘要

背景

神经胶质细胞成熟因子-γ(GMFG)通过与肌动蛋白相关蛋白 2/3 复合物(Arp2/3)结合,被报道能抑制肌动蛋白的成核。考虑到 GMFG 主要功能是在肌动蛋白重塑中发挥作用,这对免疫反应、血管生成、细胞分裂和运动至关重要,因此 GMFG 应该在肿瘤发展中具有重要作用,但到目前为止,只有两项研究描述了 GMFG 在癌症中的作用。本研究通过分析癌症基因组图谱(TCGA)数据中 GMFG 的临床价值,以及通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析来研究 GMFG 的功能机制,旨在更好地了解 GMFG 在多种癌症中的影响,并为 GMFG 的未来研究引起更多关注。

方法

从 TCGA 收集癌症患者的 RNA-seq 和临床数据,并通过 Kaplan-Meier 方法进行分析。GO 和 KEGG 分析使用在线工具数据库 for Annotation, Visualization and Integrated Discovery(DAVID)进行。

结果

与相应的正常样本相比,GMFG 在胶质母细胞瘤(GBM)、肾透明细胞癌(KIRC)、低级别胶质瘤(LGG)、急性髓系白血病(LAML)和胰腺癌(PAAD)、睾丸癌(TGCT)中显著上调,但在肾嫌色细胞癌(KICH)、肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)中下调(所有 P 值均<0.05)。GMFG 高表达预示着 GBM(HR=1.5,P=0.017)、LGG(HR=2.2,P<0.001)、LUSC(HR=1.4,P=0.022)和眼黑色素瘤(UVM)(HR=7,P<0.001)的 OS 更差,以及 LGG(HR=1.8,P<0.001)和前列腺癌(PRAD)(HR=1.9,P=0.004)的 DFS 更差。相反,GMFG 高表达与皮肤黑色素瘤(SKCM)(HR=0.59,P<0.001)和胸腺瘤(THYM)(HR=0.098,P=0.031)的 OS 更好,以及胆管癌(CHOL)(HR=0.2,P=0.003)的 DFS 更好有关。GMFG 主要参与免疫反应、蛋白结合和细胞因子-细胞因子受体相互作用途径,并且在大多数癌症中与多种免疫调节剂呈正相关。

结论

我们的研究初步表明,GMFG 通过调节肿瘤进展、免疫反应状态和组织特异性肿瘤微环境(TME),可能导致不同的癌症产生不同的存活结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2d/8052856/1a953c1a7370/12885_2021_8163_Fig1_HTML.jpg

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