Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Genes (Basel). 2023 May 26;14(6):1157. doi: 10.3390/genes14061157.
Triple-negative breast cancer (TNBC) has a very poor prognosis due to the disease's lack of established targeted treatment options. Glia maturation factor γ (GMFG), a novel ADF/cofilin superfamily protein, has been reported to be differentially expressed in tumors, but its expression level in TNBC remains unknown. The question of whether GMFG correlates with the TNBC prognosis is also unclear. In this study, data from the Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), Human Protein Atlas (HPA), and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression of GMFG in pan-cancer and the correlation between clinical factors. Gene Set Cancer Analysis (GSCA) and Gene Set Enrichment Analysis (GSEA) were also used to analyze the functional differences between the different expression levels and predict the downstream pathways. GMFG expression in breast cancer tissues, and its related biological functions, were further analyzed by immunohistochemistry (IHC), immunoblotting, RNAi, and function assay; we found that TNBC has a high expression of GMFG, and this higher expression was correlated with a poorer prognosis in TCGA and collected specimens of the TNBC. GMFG was also related to TNBC patients' clinicopathological data, especially those with histological grade and axillary lymph node metastasis. In vitro, GMFG siRNA inhibited cell migration and invasion through the EMT pathway. The above data indicate that high expression of GMFG in TNBC is related to malignancy and that GMFG could be a biomarker for the detection of TNBC metastasis.
三阴性乳腺癌(TNBC)由于缺乏既定的靶向治疗选择,预后非常差。神经胶质细胞成熟因子γ(GMFG)是一种新型 ADF/cofilin 超家族蛋白,据报道在肿瘤中存在差异表达,但在 TNBC 中的表达水平尚不清楚。GMFG 是否与 TNBC 预后相关的问题也不清楚。在这项研究中,使用了癌症基因组图谱(TCGA)、临床蛋白质组肿瘤分析联盟(CPTAC)、人类蛋白质图谱(HPA)和基因型组织表达(GTEx)数据库中的数据来分析 GMFG 在泛癌中的表达情况以及与临床因素的相关性。还使用基因集癌症分析(GSCA)和基因集富集分析(GSEA)来分析不同表达水平之间的功能差异,并预测下游途径。通过免疫组织化学(IHC)、免疫印迹、RNAi 和功能测定进一步分析了 GMFG 在乳腺癌组织中的表达及其相关的生物学功能,我们发现 TNBC 中 GMFG 表达较高,这种高表达与 TCGA 和收集的 TNBC 标本的预后较差相关。GMFG 还与 TNBC 患者的临床病理数据相关,特别是与组织学分级和腋窝淋巴结转移相关。在体外,GMFG siRNA 通过 EMT 途径抑制细胞迁移和侵袭。上述数据表明,TNBC 中 GMFG 的高表达与恶性程度有关,GMFG 可能是检测 TNBC 转移的生物标志物。