Department of Gynecology, Nanfang Hospital, Southern Medical University, No. 1838, Guang Zhou Northern Avenue, Guangzhou, 510515, China.
Department of Gynecology, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan, 030001, shanxi, China.
J Cancer Res Clin Oncol. 2023 Nov;149(16):14673-14689. doi: 10.1007/s00432-023-05267-z. Epub 2023 Aug 16.
We aimed to investigate the molecular characteristics of cervical squamous cell carcinoma (CESC) by analyzing ferroptosis-related gene (FRG) expression data to predict prognosis.
Gene expression and clinicopathological data of patients with CESC were collected from the Cancer Genome Atlas and the Genotype-Tissue Expression databases. Using Cox regression analysis, we identified 21 FRGs associated with prognosis. Cluster analysis categorized patients into subgroups based on these genes and compared their clinicopathological, biological, and immune infiltration features. FRG methylation levels were examined, and a risk model based on such FRG methylation levels was constructed using LASSO and Cox regression analyses. The model's predictive capacity was validated, and the relationships between the risk score and immune infiltration, tumor microenvironment, and drug sensitivity were explored. FRG methylation in CESC tissues was validated by immunohistochemistry.
We identified 21 FRGs associated with CESC prognosis. Patients were stratified into two subtypes based on these genes, they showed differences in prognosis, immune cell types, and immune checkpoint expression. A three-gene risk score (including AQP3, MGST1, and TFRC) was generated, and the low-risk group showed better overall survival. The high-risk and low-risk groups differed in terms of immune infiltration, gene mutations, and drug sensitivity. Experimental validation confirmed the upregulation of AQP3 and TFRC, whereas MGST1 expression was not significantly altered in CESC tissues compared with that in normal cervical tissues.
This study highlights the potential role of FRG methylation in predicting CESC prognosis and provides a personalized assessment of immune responses in patients with CESC.
通过分析铁死亡相关基因（FRG）表达数据，研究宫颈鳞状细胞癌（CESC）的分子特征，以预测预后。
从癌症基因组图谱和基因-组织表达数据库中收集了 CESC 患者的基因表达和临床病理数据。使用 Cox 回归分析，确定了与预后相关的 21 个 FRG。基于这些基因，聚类分析将患者分为亚组，并比较了它们的临床病理、生物学和免疫浸润特征。检查了 FRG 甲基化水平，并使用 LASSO 和 Cox 回归分析构建了基于这些 FRG 甲基化水平的风险模型。验证了该模型的预测能力，并探讨了风险评分与免疫浸润、肿瘤微环境和药物敏感性的关系。通过免疫组织化学验证了 CESC 组织中的 FRG 甲基化。
我们确定了与 CESC 预后相关的 21 个 FRG。根据这些基因，患者被分为两个亚组，它们在预后、免疫细胞类型和免疫检查点表达方面存在差异。生成了一个包含 3 个基因的风险评分（包括 AQP3、MGST1 和 TFRC），低风险组的总生存率更好。高风险和低风险组在免疫浸润、基因突变和药物敏感性方面存在差异。实验验证证实 AQP3 和 TFRC 的表达上调，而与正常宫颈组织相比，CESC 组织中 MGST1 的表达没有明显改变。
本研究强调了 FRG 甲基化在预测 CESC 预后中的潜在作用，并为 CESC 患者的免疫反应提供了个性化评估。
