Department of Laboratory Medicine, Lianyungang Affiliated Hospital of Nanjing University of Chinese Medicine, Lianyungang, Jiangsu, China.
Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, China.
PeerJ. 2024 Aug 6;12:e17842. doi: 10.7717/peerj.17842. eCollection 2024.
Ferroptosis is a non-apoptotic iron-dependent form of cell death implicated in various cancer pathologies. However, its precise role in tumor growth and progression of cervical cancer (CC) remains unclear. Transferrin receptor protein 1 (TFRC), a key molecule associated with ferroptosis, has been identified as influencing a broad range of pathological processes in different cancers. However, the prognostic significance of TFRC in CC remains unclear. The present study utilized bioinformatics to explore the significance of the ferroptosis-related gene TFRC in the progression and prognosis of CC.
We obtained RNA sequencing data and corresponding clinical information on patients with CC from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. Using least absolute shrinkage and selection operator (LASSO) Cox regression, we then generated a multigene signature of five ferroptosis-related genes (FRGs) for the prognostic prediction of CC. We investigated the relationship between TFRC gene expression and immune cell infiltration by employing single-sample GSEA (ssGSEA) analysis. The potential functional role of the TFRC gene was evaluated through gene set enrichment analysis (GSEA). Immunohistochemistry and qPCR was employed to assess TFRC mRNA and protein expression in 33 cases of cervical cancer. Furthermore, the relationship between TFRC mRNA expression and overall survival (OS) was investigated in patients.
CC samples had significantly higher TFRC gene expression levels than normal tissue samples. Higher TFRC gene expression levels were strongly associated with higher cancer T stages and OS events. The findings of multivariate analyses illustrated that the OS in CC patients with high TFRC expression is shorter than in patients with low TFRC expression. Significant increases were observed in the levels of TFRC mRNA and protein expression in patients diagnosed with CC.
Increased TFRC expression in CC was associated with disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration. In addition, it highlights ferroptosis as a promising therapeutic target for CC.
铁死亡是一种非凋亡性的铁依赖性细胞死亡方式，与多种癌症病理有关。然而，其在宫颈癌（CC）肿瘤生长和进展中的精确作用仍不清楚。转铁蛋白受体蛋白 1（TFRC）是与铁死亡相关的关键分子，已被确定为影响不同癌症中广泛病理过程的因素。然而，TFRC 在 CC 中的预后意义尚不清楚。本研究利用生物信息学方法探讨了铁死亡相关基因 TFRC 在 CC 进展和预后中的意义。
我们从癌症基因组图谱（TCGA）、基因型组织表达（GTEx）和基因表达综合数据库（GEO）中获得了 CC 患者的 RNA 测序数据和相应的临床信息。然后，我们使用最小绝对收缩和选择算子（LASSO）Cox 回归生成了一个由五个铁死亡相关基因（FRGs）组成的多基因signature，用于 CC 的预后预测。我们通过单样本 GSEA（ssGSEA）分析研究了 TFRC 基因表达与免疫细胞浸润的关系。通过基因集富集分析（GSEA）评估了 TFRC 基因的潜在功能作用。采用免疫组织化学和 qPCR 检测 33 例宫颈癌组织中 TFRC 基因的 mRNA 和蛋白表达。进一步研究了 TFRC mRNA 表达与患者总生存期（OS）的关系。
CC 样本中的 TFRC 基因表达水平明显高于正常组织样本。较高的 TFRC 基因表达水平与较高的癌症 T 分期和 OS 事件密切相关。多变量分析的结果表明，TFRC 高表达的 CC 患者的 OS 短于 TFRC 低表达的患者。CC 患者的 TFRC mRNA 和蛋白表达水平显著升高。
CC 中 TFRC 表达的增加与疾病进展、预后不良和免疫细胞浸润失调有关。此外，它突出了铁死亡作为 CC 有希望的治疗靶点的潜力。
