Abstract:
Ovarian cancer (OC) is a fatal gynecologic disease. The most common treatment for OC patients is surgery combined with chemotherapy but most patients at advanced stages eventually develop relapse due to chemoresistance. This study examined the role and function of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in OC. We observed that the expression of IGF2BP2 mRNA and protein was up-regulated in OC cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. An increase in IGF2BP2 expression at mRNA and protein levels was verified by the analyses of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), respectively. Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were applied to analyze the expression and clinical value of IGF2BP2. Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses explored biological functions and the involvement of IGF2BP2 in cell growth. Indeed, the knockdown of IGF2BP2 resulted in the inhibition of OC cell proliferation evaluated by the Cell Counting Kit-8 assay. Genomic amplification of IGF2BP2 partly accounted for its overexpression. High expression of IGF2BP2 was associated with signal transducer and activator of transcription 1 (STAT1) and drug sensitivity and was correlated with an unfavorable survival outcome in OC patients. Furthermore, the responsiveness of chemotherapy and immunotherapy were analyzed using the \"pRRophetic\" R package and The Cancer Immune Atlas (TCIA) database, respectively. The low expression of IGF2BP2 was associated with chemoresistance but with high tumor microenvironment scores and tumor-infiltrating immune cells, suggesting that immunotherapy may apply in chemoresistant patients. The alteration of IGF2BP2 expression may respond to chemotherapy and immunotherapy. Thus, IGF2BP2 shows potential as a therapeutic target and diagnostic biomarker for OC.
摘要:
卵巢癌(OC)是一种致命的妇科疾病。OC患者最常见的治疗方法是手术联合化疗,但大多数晚期患者最终因化疗耐药而复发。这项研究检查了胰岛素样生长因子2mRNA结合蛋白2(IGF2BP2)在OC中的作用和功能。我们观察到IGF2BP2mRNA和蛋白的表达在OC细胞和组织中通过定量实时聚合酶链反应(qRT-PCR)和westernblot,分别。通过癌症基因组图谱(TCGA)和临床蛋白质组学肿瘤分析联盟(CPTAC)的分析,证实了IGF2BP2在mRNA和蛋白质水平的表达增加。分别。应用基因表达综合(GEO)和癌细胞系百科全书(CCLE)数据库分析IGF2BP2的表达和临床价值。基因集富集分析(GSEA),京都基因和基因组百科全书(KEGG),和基因本体论(GO)分析探讨了生物学功能和IGF2BP2在细胞生长中的参与。的确,IGF2BP2的敲低导致通过细胞计数试剂盒-8测定评价的OC细胞增殖的抑制。IGF2BP2的基因组扩增部分解释了其过度表达。IGF2BP2的高表达与信号转导和转录激活因子1(STAT1)和药物敏感性相关,并且与OC患者的不良生存结局相关。此外,使用“pRrophetic”R包和癌症免疫图谱(TCIA)数据库分析化疗和免疫治疗的反应性,分别。IGF2BP2的低表达与化疗耐药有关,但与高肿瘤微环境评分和肿瘤浸润免疫细胞有关。表明免疫疗法可能适用于化疗耐药患者。IGF2BP2表达的改变可能对化疗和免疫疗法有反应。因此,IGF2BP2显示出作为OC的治疗靶标和诊断生物标志物的潜力。