PAX1低甲基化作为宫颈癌放射耐药的预后生物标志物。

IF 5.7 2区 医学 Q1 Medicine
Xuanxuan Li, Huan Liu, Xue Zhou, Yangying Zhou, Yu Zhang, Yu-Ligh Liou, Manting Zeng, Hong Zhu
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引用次数: 0

摘要

背景:PAX1基因甲基化在宫颈癌的发生发展中起重要作用。但其在局部晚期宫颈癌放疗后的预后价值尚不清楚,因此本研究旨在探讨PAX1基因甲基化对宫颈癌放疗敏感性的预测价值。方法:选择125例同步放化疗的原发性宫颈癌患者作为研究人群,采用定量甲基化特异性聚合酶链反应(QMSP)检测宫颈脱落细胞PAX1甲基化状态。采用Logistic回归模型分析影响短期疗效的危险因素,建立基于PAX1基因甲基化的放疗敏感性预测模型。用CCK8评价转染PAX1或对照载体的Hela和SiHa细胞辐照后的细胞活力。此外,RNA-Seq分析在PAX1过表达的SiHa细胞中鉴定了不同的表达基因(DEGs)。通过基因本体(Gene Ontology, GO)和途径富集分析来确定DEGs的生物学功能。结果:PAX1甲基化水平与hpv16 /18阳性率相关。PAX1低甲基化被发现是化疗后肿瘤残留的危险因素。进一步构建包含PAX1甲基化状态、淋巴结转移、病理类型和肿瘤大小等危险因素的nomogram预测放化疗后肿瘤残留概率(AUC = 0.823, 95% CI 0.736-0.910)。高PAX1蛋白水平更容易引起Hela和SiHa细胞的辐射抗性。PAX1过表达细胞和对照细胞转录组测序鉴定出615个差异表达基因,GO富集分析提示PAX1可能参与信号受体活性调控和病毒应答。结论:PAX1低甲基化状态可作为预测宫颈癌放射耐药的生物标志物。这进一步为宫颈癌同步放疗的个体化治疗策略提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PAX1 hypomethylation as a prognostic biomarker for radioresistance of cervical cancer.

PAX1 hypomethylation as a prognostic biomarker for radioresistance of cervical cancer.

PAX1 hypomethylation as a prognostic biomarker for radioresistance of cervical cancer.

PAX1 hypomethylation as a prognostic biomarker for radioresistance of cervical cancer.

Background: PAX1 gene methylation plays an important role in the development of cervical cancer. However, its prognostic value after radiotherapy for locally advanced cervical cancer is unknown, so this study aimed to investigate the value of PAX1 gene methylation for predicting the sensitivity of radiotherapy for cervical cancer.

Methods: We selected 125 patients with primary cervical cancer who underwent concurrent chemo-radiotherapy as the study population, quantitative methylation-specific polymerase chain reaction (QMSP) was used for detecting PAX1 methylation status of cervical exfoliated cells. Logistic regression model was used to analyze the risk factors associated with the short-term efficacy and to establish a prediction model of radiotherapy sensitivity based on PAX1 gene methylation. Cell viability after radiation of Hela and SiHa cells transfected with PAX1 or control vector was evaluated by CCK8. Furthermore, RNA-Seq analyses identified different expressed genes (DEGs) in PAX1 overexpressed SiHa cells. Gene Ontology (GO) and pathway enrichment analysis was carried out to determine the biological function of DEGs.

Results: PAX1 methylation level was associated with HPV16/18-positive rate. PAX1 hypomethylation was found to be a risk factor for tumor residual after chemo-radiotherapy. A nomogram containing the risk factors for PAX1 methylation status, lymph node metastasis, pathological type and tumor size was further constructed to predict the probability of tumor residual after chemo-radiotherapy (AUC = 0.823, 95% CI 0.736-0.910). High PAX1 protein level was more likely to cause radioresistance in both Hela and SiHa cells. Transcriptomic sequencing of PAX1 overexpressed and control cells identified 615 differentially expressed genes, and GO enrichment analysis suggested that PAX1 may be involved in the regulation of signaling receptor activity and response to viruses.

Conclusion: PAX1 hypomethylation status could be used as a promising biomarker to predict radioresistance in cervical cancer. This further provides a new idea for the individualized treatment strategy of simultaneous radiotherapy for cervical cancer.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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