Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, 310016, China.
J Ovarian Res. 2024 Mar 16;17(1):64. doi: 10.1186/s13048-024-01386-4.
BACKGROUND: Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. METHODS: The present study used the differentially expressed genes (DEGs) obtained from the "Limma" package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified-claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)-by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity. RESULTS: The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion. CONCLUSION: IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.
背景:卵巢癌(OC)是一种严重的妇科恶性肿瘤,具有重大的诊断和治疗挑战。发现可靠的癌症生物标志物可用于调整诊断并改善患者的护理。然而,浆液性 OC 缺乏有效的生物标志物。我们旨在确定 OC 的新型生物标志物及其发病原因。
方法:本研究使用来自“Limma”软件包和 WGCNA 模块的差异表达基因(DEGs)进行交集分析,以获得 OC 中的 DEGs。通过搜索 PPI 网络中的枢纽基因并在 GSE14407、GSE18520、GSE66957 和 TCGA+GTEx 数据库中进行验证,确定了三个枢纽基因-紧密连接蛋白 3(CLDN3)、干扰素调节因子 6(IRF6)和蛋白酶 8(PRSS8)。在 Kaplan-Meier Plotter 中进一步确认了 IRF6 与 OC 患者预后的相关性。RT-qPCR 和 IHC 验证了 OC 样本中 IRF6 的 RNA 和蛋白水平。使用 Transwell 侵袭和划痕实验探讨了 IRF6 对 OC 的影响。最后,构建了枢纽基因的 ceRNA 网络,并使用生物信息学工具预测药物敏感性。
结果:TCGA、GTEx 和 GEO 数据库的联合分析结果表明,IRF6 RNA 和蛋白水平在浆液性 OC 中显著上调,与 OS 和 PFS 相关。细胞功能实验表明,IRF6 敲低抑制 SKOV3 细胞增殖、迁移和侵袭。
结论:IRF6 与 OC 的发生发展密切相关,可作为 OC 患者的新型生物标志物和治疗靶点。
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