Wang Jing, An Wen, Pang Ziyao, Zhao Manyin, Xu Anli, Zhao Junwei
Department of Gynaecology, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, Shandong, China.
Department of Pathology, Tonglu First People's Hospital, Hangzhou, China.
Front Oncol. 2025 Apr 15;15:1523137. doi: 10.3389/fonc.2025.1523137. eCollection 2025.
Early detection and treatment of CIN or early-stage cervical cancer lead to better clinical outcomes compared to treating advanced-stage patients. Thus, specific biomarkers for the diagnosis and prognosis of CIN and early-stage cervical cancer should be urgently explored.
We analyzed tumor based on genes closely related to OS in the database with GSE63514, GSE7803, GSE9750 and TCGA data sets, the top 20 core genes were screened out. Notably, transferrin receptor (TFRC) emerged as a prioritized candidate due to its dual role in cellular iron homeostasis and oncogenic signaling. However, the exact role of TFRC in the development and progression of cervical cancer remains unclear. We then used various bioinformatics methods and mathematical models to analyze those data, aiming to investigate the clinical significance of TFRC in cervical cancer and illustrate its association with tumor immunity. In addition, the molecular function and mechanisms of TFRC were revealed by gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. Immunohistochemistry was employed to assess TFRC protein expression in 19 cervical cancers, 16 HSILs and 15 normal cervical tissues.
TFRC was highly expressed in CESC in the TCGA and GSE9750 datasets. Meanwhile, the expression of TFRC was correlated with pathological stage, lymph node metastasis, malignant degree of cervical lesions and HPV infection status. Our analysis confirmed that TFRC expression was higher in CESC tissues compared to normal cervical tissues, and it was also elevated in HSIL relative to normal tissues, as determined by IHC staining. Increased TFRC expression was linked to decreased overall survival (OS) ( = 0.024), disease-specific survival (DSS) ( = 0.009), and progression-free interval (PFI) ( = 0.007) in CESC patients. In different clinical stages, pathological T stages, and pathological N stages, higher TFRC expression was significantly associated with worse survival for OS and DSS. We constructed a nomogram model, TFRC contributed significantly to the prognosis and exhibited good predictive power for the OS and the DSS. Finally, we confirmed that immunosuppression in cervical cancer is closely related to high TFRC expression.
TFRC exhibits significant diagnostic and prognostic value in cervical cancer.
与晚期宫颈癌患者的治疗相比，早期发现并治疗宫颈上皮内瘤变（CIN）或早期宫颈癌可带来更好的临床结局。因此，迫切需要探索用于CIN和早期宫颈癌诊断及预后评估的特异性生物标志物。
我们基于与总生存期（OS）密切相关的基因，对数据库中的GSE63514、GSE7803、GSE9750数据集以及癌症基因组图谱（TCGA）数据进行肿瘤分析，筛选出前20个核心基因。值得注意的是，转铁蛋白受体（TFRC）因其在细胞铁稳态和致癌信号传导中的双重作用，成为优先候选基因。然而，TFRC在宫颈癌发生发展过程中的确切作用仍不清楚。随后，我们运用多种生物信息学方法和数学模型对这些数据进行分析，旨在探究TFRC在宫颈癌中的临床意义，并阐明其与肿瘤免疫的关联。此外，通过基因本体论、京都基因与基因组百科全书以及基因集富集分析揭示了TFRC的分子功能及机制。采用免疫组织化学方法评估19例宫颈癌、16例高级别鳞状上皮内病变（HSIL）和15例正常宫颈组织中TFRC蛋白的表达情况。
在TCGA和GSE9750数据集中，TFRC在宫颈鳞状细胞癌（CESC）中高表达。同时，TFRC的表达与病理分期、淋巴结转移、宫颈病变恶性程度及人乳头瘤病毒（HPV）感染状态相关。我们的分析证实，通过免疫组化染色发现，CESC组织中TFRC的表达高于正常宫颈组织，HSIL中TFRC的表达相对于正常组织也有所升高。CESC患者中，TFRC表达升高与总生存期（OS）降低（P = 0.024）、疾病特异性生存期（DSS）降低（P = 0.009）和无进展生存期（PFI）降低（P = 0.007）相关。在不同临床分期、病理T分期和病理N分期中，较高的TFRC表达与OS和DSS的较差生存显著相关。我们构建了一个列线图模型，TFRC对预后有显著贡献，对OS和DSS具有良好的预测能力。最后，我们证实宫颈癌中的免疫抑制与高TFRC表达密切相关。
TFRC在宫颈癌中具有显著的诊断和预后价值。
