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系统分析可变剪接特征揭示宫颈癌的预后预测因子。

Systematic profiling of alternative splicing signature reveals prognostic predictor for cervical cancer.

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, 110004, China.

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

出版信息

J Transl Med. 2019 Nov 19;17(1):379. doi: 10.1186/s12967-019-02140-x.

Abstract

AIM

Cervical cancer is a common malignant carcinoma of the gynecological tract with high morbidity and mortality. Therefore, it is crucial to elucidate the pathogenesis, prevention, diagnosis and prognosis of cervical cancer by searching for the involved key genes.

METHOD

In this study, the alternative splicing (AS) events of 253 patients with cervical cancer were analyzed, and 41,766 AS events were detected in 9961 genes. Univariate analysis was performed to screen prognostic AS events. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to identify the pathways in which these AS events were involved.

RESULTS

We found that exon skip (ES) is the main AS event in patients with cervical cancer. There was pronounced consistency between the genes involved in overall survival and those involved in recurrence. At the same time, we found that a gene may exhibit several different types of AS events, and these different AS events may be related to prognosis. Four characteristic genes, HSPA14, SDHAF2, CAMKK2 and TM9SF1, that can be used as prognostic markers for cervical cancer were selected.

CONCLUSION

The importance of AS events in the development of cervical cancer and prediction of prognosis was revealed by a large amount of data at the whole genome level, which may provide a potential target for cervical cancer treatment. We also provide a new method for exploring the pathogenesis of cervical cancer to determine clinical treatment and prognosis more accurately.

摘要

目的

宫颈癌是一种常见的妇科恶性癌,发病率和死亡率都很高。因此,通过寻找相关的关键基因,阐明宫颈癌的发病机制、预防、诊断和预后至关重要。

方法

本研究分析了 253 例宫颈癌患者的选择性剪接(AS)事件,在 9961 个基因中检测到 41766 个 AS 事件。通过单因素分析筛选出与预后相关的 AS 事件。京都基因与基因组百科全书(KEGG)富集分析用于识别这些 AS 事件所涉及的途径。

结果

我们发现外显子跳跃(ES)是宫颈癌患者中主要的 AS 事件。总体生存和复发相关的基因之间存在明显的一致性。同时,我们发现一个基因可能表现出几种不同类型的 AS 事件,这些不同的 AS 事件可能与预后有关。选择了四个特征基因 HSPA14、SDHAF2、CAMKK2 和 TM9SF1,它们可作为宫颈癌的预后标志物。

结论

大量全基因组数据揭示了 AS 事件在宫颈癌发生发展和预后预测中的重要性,可能为宫颈癌的治疗提供潜在的靶点。我们还提供了一种新的方法来探索宫颈癌的发病机制,以更准确地确定临床治疗和预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20d8/6865056/850451991624/12967_2019_2140_Fig1_HTML.jpg

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