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通过生物信息学鉴定宫颈癌放疗抵抗相关关键基因

Identification of critical genes associated with radiotherapy resistance in cervical cancer by bioinformatics.

作者信息

Zhang Zhenhua, Xiang Kechao, Tan Longjing, Du Xiuju, He Huailin, Li Dan, Li Li, Wen Qinglian

机构信息

The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Guangxi Medical University Cancer Hospital, Nanning, China.

出版信息

Front Oncol. 2022 Jul 29;12:967386. doi: 10.3389/fonc.2022.967386. eCollection 2022.

Abstract

BACKGROUND

Cervical cancer (CC) is one of the common malignant tumors in women, Currently, 30% of patients with intermediate to advanced squamous cervical cancer are still uncontrolled or recurrent after standard radical simultaneous radiotherapy; therefore, the search for critical genes affecting the sensitivity of radiotherapy may lead to new strategies for treatment.

METHODS

Firstly, differentially expressed genes (DEGs) between radiotherapy-sensitivity and radiotherapy-resistance were identified by GEO2R from the gene expression omnibus (GEO) website, and prognosis-related genes for cervical cancer were obtained from the HPA database. Subsequently, the DAVID database analyzed gene ontology (GO). Meanwhile, the protein-protein interaction network was constructed by STRING; By online analysis of DEGs, prognostic genes, and CCDB data that are associated with cervical cancer formation through the OncoLnc database, we aim to search for the key DEGs associated with CC, Finally, the key gene(s) was further validated by immunohistochemistry.

RESULT

298 differentially expressed genes, 712 genes associated with prognosis, and 509 genes related to cervical cancer formation were found. The results of gene function analysis showed that DEGs were mainly significant in functional pathways such as variable shear and energy metabolism. By further verification, two genes, ASPH and NKAPP1 were identified through validation as genes that affect both sensitivities to radiotherapy and survival finally. Then, immunohistochemical results showed that the ASPH gene was highly expressed in the radiotherapy-resistant group and had lower Overall survival (OS) and Progression-free survival (PFS).

CONCLUSION

This study aims to better understand the characteristics of cervical cancer radiation therapy resistance-related genes through bioinformatics and provide further research ideas for finding new mechanisms and potential therapeutic targets related to cervical cancer radiation therapy.

摘要

背景

宫颈癌(CC)是女性常见的恶性肿瘤之一。目前,30%的中晚期宫颈鳞状细胞癌患者在标准根治性同步放疗后仍未得到控制或复发;因此,寻找影响放疗敏感性的关键基因可能会带来新的治疗策略。

方法

首先,通过GEO2R从基因表达综合数据库(GEO)网站中鉴定放疗敏感性和放疗抗性之间的差异表达基因(DEG),并从人类蛋白质图谱(HPA)数据库中获取宫颈癌的预后相关基因。随后,利用DAVID数据库分析基因本体(GO)。同时,通过STRING构建蛋白质-蛋白质相互作用网络;通过OncoLnc数据库对与宫颈癌形成相关的DEG、预后基因和CCDB数据进行在线分析,旨在寻找与CC相关的关键DEG,最后通过免疫组织化学进一步验证关键基因。

结果

发现了298个差异表达基因、712个与预后相关的基因和509个与宫颈癌形成相关的基因。基因功能分析结果表明,DEG主要在可变剪接和能量代谢等功能途径中具有显著性。通过进一步验证,最终确定了两个基因ASPH和NKAPP1,它们既影响放疗敏感性又影响生存率。然后,免疫组织化学结果显示,ASPH基因在放疗抗性组中高表达,总生存期(OS)和无进展生存期(PFS)较低。

结论

本研究旨在通过生物信息学更好地了解宫颈癌放疗抗性相关基因的特征,并为寻找与宫颈癌放疗相关的新机制和潜在治疗靶点提供进一步的研究思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7db/9373049/f4c61568a25d/fonc-12-967386-g001.jpg

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