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共表达网络分析确定了Krüppel样因子6(KLF6)与卵巢癌化疗敏感性的关联。

Coexpression network analysis identified Krüppel-like factor 6 (KLF6) association with chemosensitivity in ovarian cancer.

作者信息

Chen Ying, Bi Fangfang, An Yuanyuan, Yang Qing

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

J Cell Biochem. 2019 Feb;120(2):2607-2615. doi: 10.1002/jcb.27567. Epub 2018 Sep 11.

Abstract

Although most patients with ovarian cancer (OC) are initially sensitive to paclitaxel/carboplatin combination chemotherapy, eventually they develop resistance to chemotherapy drugs and experience disease relapse. OC is the most lethal gynecological malignancy, and the five-year survival rate is extremely low. Thus, research on specific biomarkers and potential targets for chemotherapy-resistant patients with OC is needed. In our study, genes in the top 10% of variance in data set GSE30161 from chemoresistant and chemosensitive OC tissues were determined to conduct a weighted gene coexpression network analysis (WGCNA). The magenta module was most strongly related to OC chemoresponse. Gene ontology enrichment analysis indicated that the function of the magenta module primarily focused on transcription regulation, cell cycle control, and apoptosis modulation. Integration of the WGCN with the protein-protein interaction network identified five candidate genes. These five genes were verified using the GSE51373 test set, and Krüppel-like factor 6 ( KLF6) was identified as tightly linked to OC chemosensitivity. The receiver operating characteristic (ROC) curve showed that KLF6 differentiated chemoresistant from chemosensitive OC tissues. The Kaplan-Meier online database indicated that high KLF6 expression was associated with poor OC prognosis. Gene set enrichment analysis determined that the KLF6 mechanism was potentially associated with cell cycle, mTOR, and DNA-damage repair signaling pathways. In conclusion, KLF6 was identified in association with OC chemoresistance, and the mechanism of KLF6-mediated chemoresistance may involve the cell cycle, mTOR, and DNA-damage repair signaling pathways.

摘要

尽管大多数卵巢癌(OC)患者最初对紫杉醇/卡铂联合化疗敏感,但最终他们会对化疗药物产生耐药性并经历疾病复发。OC是最致命的妇科恶性肿瘤,五年生存率极低。因此,需要对OC化疗耐药患者的特定生物标志物和潜在靶点进行研究。在我们的研究中,确定了来自化疗耐药和化疗敏感OC组织的数据集GSE30161中变异排名前10%的基因,以进行加权基因共表达网络分析(WGCNA)。品红色模块与OC化疗反应的相关性最强。基因本体富集分析表明,品红色模块的功能主要集中在转录调控、细胞周期控制和凋亡调节。将WGCN与蛋白质-蛋白质相互作用网络整合,鉴定出五个候选基因。使用GSE51373测试集对这五个基因进行了验证,并且鉴定出Krüppel样因子6(KLF6)与OC化疗敏感性紧密相关。受试者工作特征(ROC)曲线表明,KLF6能够区分化疗耐药和化疗敏感的OC组织。Kaplan-Meier在线数据库表明,高KLF6表达与OC预后不良相关。基因集富集分析确定,KLF6机制可能与细胞周期、mTOR和DNA损伤修复信号通路有关。总之,鉴定出KLF6与OC化疗耐药相关,并且KLF6介导的化疗耐药机制可能涉及细胞周期、mTOR和DNA损伤修复信号通路。

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