Department of Oncology, Xiangya Hospital, Central South University, Hunan, 410008, China.
Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Hunan, 410008, China.
Clin Epigenetics. 2023 Aug 2;15(1):123. doi: 10.1186/s13148-023-01538-1.
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.
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.
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.
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.
PAX1 基因甲基化在宫颈癌的发生发展中起着重要作用。然而，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 基因甲基化预测宫颈癌放疗敏感性的价值。
我们选择了 125 例接受同期放化疗的原发性宫颈癌患者作为研究对象，采用定量甲基化特异性聚合酶链反应（QMSP）检测宫颈脱落细胞中 PAX1 甲基化状态。采用 Logistic 回归模型分析与近期疗效相关的危险因素，并建立基于 PAX1 基因甲基化的放疗敏感性预测模型。用 CCK8 评估转染 PAX1 或对照载体的 Hela 和 SiHa 细胞在辐射后的细胞活力。此外，通过 RNA-Seq 分析鉴定了 PAX1 过表达 SiHa 细胞中的差异表达基因（DEGs）。进行基因本体论（GO）和通路富集分析，以确定 DEGs 的生物学功能。
PAX1 甲基化水平与 HPV16/18 阳性率相关。PAX1 低甲基化被发现是放化疗后肿瘤残留的危险因素。进一步构建了包含 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列线图，以预测放化疗后肿瘤残留的概率（AUC=0.823，95%CI 0.736-0.910）。PAX1 蛋白高表达在 Hela 和 SiHa 细胞中更可能导致放射抵抗。PAX1 过表达和对照细胞的转录组测序鉴定出 615 个差异表达基因，GO 富集分析表明 PAX1 可能参与调节信号受体活性和对病毒的反应。
PAX1 低甲基化状态可作为预测宫颈癌放疗抵抗的有前途的生物标志物。这为宫颈癌同期放化疗的个体化治疗策略提供了新的思路。
