Yang Xiaocheng, Yin Fanxing, Liu Qingyang, Ma Yue, Zhang Hao, Guo Panpan, Wen Wen, Guo Xu, Wu Yihao, Yang Zhuo, Han Yanshuo
School of Life and Pharmaceutical Sciences, Dalian University of Technology, Dalian, China.
Department of Gynecology, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang, China.
Ann Transl Med. 2022 Jan;10(2):123. doi: 10.21037/atm-21-6265.
Cervical cancer (CC) is a disease that affects female health; therefore, timely prevention and diagnosis of CC are crucial to decrease its mortality. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is involved in tumor progression. However, the role of ferroptosis-related genes (FRGs) in the immune microenvironment of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) remains unclear.
The data sets of CESC patients, including RNA sequencing (RNA-seq) data and clinical information, were obtained from The Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was used to determine the stromal score, immune score, estimate score, and tumor purity in the CESC patients' data. Additionally, FRGs were identified and used to construct a signature marker for the diagnosis and prognosis of CESC. Patients were assigned to a high- or low-risk group based on their median risk score. The tumor microenvironment (TME), immune infiltration, and functional enrichment were compared between the low- and high-risk groups. Functional analyses, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and single-sample Gene Set Enrichment Analysis (ssGSEA), were conducted to explore the underlying mechanisms in the development and prognosis of CESC.
The results showed that the estimate score was suitable for predicting the prognosis of CESC patients. Additionally, a prediction model involving four FRGs [phosphatidylethanolamine-binding protein 1 (), dual oxidase 1 (), iron-sulfur cluster assembly enzyme (), and cytochrome b (-245) beta subunit ()] was constructed. The performance of the prognostic model and significant clinical characteristics in predicting CESC prognosis was subsequently validated. Our results showed that the expression of affected immune cells. Gene functional enrichment analyses showed that these differentially expressed FRGs were mainly enriched in the immunity-related signaling pathways, which indicated that FRGs might affect the development and prognosis of CC by regulating the immune microenvironment.
The expression profiles of FRGs are closely related to the TME and the prognostic survival of CESC patients. The interaction between ferroptosis and immunity in the development of CC provides new insight into the molecular mechanisms of CC.
宫颈癌（CC）是一种影响女性健康的疾病；因此，及时预防和诊断CC对于降低其死亡率至关重要。铁死亡是一种铁依赖性的非凋亡性细胞死亡形式，参与肿瘤进展。然而，铁死亡相关基因（FRGs）在宫颈鳞状细胞癌和宫颈内膜腺癌（CESC）免疫微环境中的作用仍不清楚。
从癌症基因组图谱（TCGA）获得CESC患者的数据集，包括RNA测序（RNA-seq）数据和临床信息。使用ESTIMATE算法确定CESC患者数据中的基质评分、免疫评分、估计评分和肿瘤纯度。此外，鉴定FRGs并用于构建CESC诊断和预后的特征标志物。根据患者的中位风险评分将其分为高风险组或低风险组。比较低风险组和高风险组之间的肿瘤微环境（TME）、免疫浸润和功能富集情况。进行功能分析，包括基因本体（GO）分析、京都基因与基因组百科全书（KEGG）分析和单样本基因集富集分析（ssGSEA），以探索CESC发生发展和预后的潜在机制。
结果表明，估计评分适用于预测CESC患者的预后。此外，构建了一个包含四个FRGs的预测模型，即磷脂酰乙醇胺结合蛋白1（ ）、双氧化酶1（ ）、铁硫簇组装酶（ ）和细胞色素b（-245）β亚基（ ）。随后验证了预后模型的性能以及预测CESC预后的显著临床特征。我们的结果表明， 的表达影响免疫细胞。基因功能富集分析表明，这些差异表达的FRGs主要富集在免疫相关信号通路中，这表明FRGs可能通过调节免疫微环境影响CC的发生发展和预后。
FRGs的表达谱与CESC患者的TME和预后生存密切相关。CC发生发展过程中铁死亡与免疫之间的相互作用为CC的分子机制提供了新的见解。
