Identification and Experimental Validation of Prognostic miRNA Signature and Ferroptosis-Related Key Genes in Cervical Squamous Cell Carcinoma

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-11-11 DOI:10.1002/cam4.70415

Yan Guo, Yana Han, Junjie Zhang, Yanbin Zhou, Meiyan Wei, Lijun Yu

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Abstract

Objectives

This study aimed to investigate the prognostic value of miRNAs and ferroptosis-related genes in cervical squamous cell carcinoma.

Methods

We mined data from public databases for differentially expressed miRNAs, ferroptosis-related genes, and clinical parameters and constructed a prognostic risk model. The predictive performance of the model was evaluated using survival and receiver operating characteristic curve analyses. We combined the clinicopathological features to construct a nomogram and evaluated its efficacy using calibration and clinical decision curves. The correlation between miRNA characteristics, risk score, and the tumor microenvironment was also studied. Next, consensus and key genes were screened, and their biological functions were analyzed using KEGG, GO, GSEA, and drug sensitivity analysis. Finally, the expression of miRNAs and key genes was detected using qRT-PCR and western blotting to verify the prediction results.

Results

Seven miRNA signatures (miR-100-3p, miR-301a-5p, miR-331-3p, miR-425-5p, miR-502-3p, miR-505-5p, and miR-629-3p) were generated, and prognostic risk and nomogram models were successfully constructed. These models exhibited good accuracy. miRNA signatures correlated with the tumor microenvironment. Twelve consensus genes and three key genes (SLC2A1, ANO6, and TXNIP) were screened and their biofunctional diversity was identified using various analytical methods. qRT-PCR and western blotting were used to verify the expression of miR-301a-5p, miR-505-5p, SLC2A1, and TXNIP in cervical squamous carcinoma. The results were consistent with those of bioinformatics analyses.

Conclusions

Seven miRNAs may serve as prognostic biomarkers of cervical squamous cell carcinoma. SLC2A1, ANO6, and TXNIP are associated with cervical squamous cell carcinoma and may serve as ferroptosis-related markers of the disease.

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宫颈鳞状细胞癌中预后 miRNA 标志和铁突变相关关键基因的鉴定与实验验证

研究目的本研究旨在探讨宫颈鳞状细胞癌中miRNAs和铁蛋白相关基因的预后价值：我们从公共数据库中挖掘了差异表达的 miRNAs、铁蛋白相关基因和临床参数，并构建了一个预后风险模型。利用生存率和接收者操作特征曲线分析评估了该模型的预测性能。我们结合临床病理特征构建了一个提名图，并利用校准和临床决策曲线评估了其有效性。我们还研究了 miRNA 特征、风险评分和肿瘤微环境之间的相关性。接着，筛选了共识基因和关键基因，并利用 KEGG、GO、GSEA 和药物敏感性分析对其生物学功能进行了分析。最后，利用qRT-PCR和Western印迹技术检测了miRNA和关键基因的表达，以验证预测结果：结果：产生了七个 miRNA 标志（miR-100-3p、miR-301a-5p、miR-331-3p、miR-425-5p、miR-502-3p、miR-505-5p 和 miR-629-3p），并成功构建了预后风险模型和提名图模型。这些模型表现出良好的准确性。利用多种分析方法筛选了 12 个共识基因和 3 个关键基因（SLC2A1、ANO6 和 TXNIP），并确定了它们的生物功能多样性。结果与生物信息学分析结果一致：结论：七种 miRNA 可作为宫颈鳞状细胞癌的预后生物标志物。SLC2A1、ANO6和TXNIP与宫颈鳞状细胞癌相关，可作为该疾病的铁突变相关标志物。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.