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转铁蛋白受体相关的低氧诱导因子-1 信号通路在宫颈癌中的作用

Transferrin receptor-involved HIF-1 signaling pathway in cervical cancer.

机构信息

Department of Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, 210008, Nanjing, China.

Department of Gynecology, Nanjing Drum Tower Hospital, Affiliated to Nanjing University Medical School, 210008, Nanjing, China.

出版信息

Cancer Gene Ther. 2019 Nov;26(11-12):356-365. doi: 10.1038/s41417-019-0078-x. Epub 2019 Jan 17.

DOI:10.1038/s41417-019-0078-x
PMID:30651591
Abstract

Cervical cancer is one of the most prevalent gynecologic malignancies and has remained an intractable cancer over the past decades. We analyzed the aberrant expression patterns of cervical cancer using RNA-Seq data from The Cancer Genome Atlas (TCGA). A total of 3352 differently expressed genes (DEGs) were identified in 306 cervical cancer samples compared with 3 control samples, with 1401 genes upregulated and 1951 downregulated. Under Kaplan-Meier analysis, 76 out of these DEGs with a significantly different survival rate between patients with high and low expression groups were picked out and uploaded to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, which identified a transferrin receptor (TFRC)-involved HIF-1 signaling pathway (p < 0.05). Clinical data analysis showed that high TFRC expression in cervical cancers was associated with incrementally advanced stage, tumor status, and lymph nodes (all p-values <0.05), while multivariate analysis revealed that TFRC remained an independent prognostic variable for poor overall survival. In conclusion, our data indicated that the TFRC-involved HIF-1 signaling pathway may play a crucial role in cervical cancer.

摘要

宫颈癌是最常见的妇科恶性肿瘤之一,在过去几十年中一直是一种难以治愈的癌症。我们使用来自癌症基因组图谱(TCGA)的 RNA-Seq 数据分析了宫颈癌的异常表达模式。在 306 例宫颈癌样本与 3 例对照样本的比较中,共鉴定出 3352 个差异表达基因(DEGs),其中 1401 个基因上调,1951 个基因下调。在 Kaplan-Meier 分析中,从这些具有高低表达组患者之间显著不同生存率的 DEGs 中挑选出 76 个,并上传进行京都基因与基因组百科全书(KEGG)通路富集分析,确定了一个转铁蛋白受体(TFRC)参与的 HIF-1 信号通路(p < 0.05)。临床数据分析表明,宫颈癌中 TFRC 的高表达与不断进展的分期、肿瘤状态和淋巴结转移有关(所有 p 值均<0.05),而多变量分析表明 TFRC 仍然是总体生存不良的独立预后变量。总之,我们的数据表明,TFRC 参与的 HIF-1 信号通路可能在宫颈癌中发挥关键作用。

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