Dai Yonggang, Li Chunxiang, Cheng Shiliang, Wang Hongya, Zhuang Xuewei
Department of Clinical Laboratoryaboratory, Shandong Provincial Third Hospital, Shandong University, No.11 Middle Wuyingshan Road, Tianqiao, Jinan, 250031, Shandong, China.
College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Sci Rep. 2025 Feb 12;15(1):5228. doi: 10.1038/s41598-025-89746-y.
Cervical cancer(CCa) remains a significant global public health concern, with early diagnosis and treatment being crucial. Moreover, the molecular mechanisms underlying its pathogenesis remain incompletely elucidated. F2RL1 is closely associated with various tumors. However, its relationship with CCa is poorly understood. We accessed data from 309 patients diagnosed with CCa from TCGA database. The Limma package facilitated differential expression analysis to identify differentially expressed mRNAs (DEmRNAs). Survival analysis and ROC analysis were conducted via the XIANTAO database. Immune-related genes were identified with F2RL1-related genes through ImmPort database analysis. Functional enrichment analysis was carried out using GO, KEGG, and GSEA. We gathered cervical cells and serum from participants to test for HPV and TCT, and then used qPCR to check the levels of F2RL1 mRNA expression. We also verified the expression of F2RL1 protein through WB and ELISA techniques. Our investigation has unveiled a fascinating discovery-the levels of F2RL1 expression in CCa tissues are notably elevated when compared to normal tissues, showcasing intriguing variations among various pathological types. Moreover, the presence of high F2RL1 expression is linked to reduce Overall Survival (OS), Progression Free Interval (PFI), Progression Free Survival (PFS). F2RL1 rocked the ROC analysis with an AUC of 0.996. Furthermore, F2RL1 expression levels significantly impact CCa in different N stages, pathological tissue types, treatment statuses, and racial groups, allowing us to develop a predictive model. Additionally, we identified 43 immune-related genes. Enrichment analysis highlighting their association with pathways related to cell movement and T cell activation. Through analysis, we discovered an inverse proportion between F2RL1 expression and the infiltration of most immune cells, particularly TFH and cytotoxic cells, suggesting a potential link to immune evasion in CCa. Molecular biology experiments also confirmed a significant increase in F2RL1 expression in cervical exfoliated cells and serum. Our research uncovers the predictive and early detection significance of F2RL1 in CCa and its correlation with immune infiltration for the first time. F2RL1 is strongly linked to the progression of CCa and could serve as a biomarker for the early diagnosis and prognosis of CCa patients.
宫颈癌（CCa）仍然是一个重大的全球公共卫生问题，早期诊断和治疗至关重要。此外，其发病机制的分子机制仍未完全阐明。F2RL1与多种肿瘤密切相关。然而，其与宫颈癌的关系却知之甚少。我们从TCGA数据库中获取了309例被诊断为宫颈癌患者的数据。Limma软件包有助于进行差异表达分析，以识别差异表达的mRNA（DEmRNAs）。通过仙桃数据库进行生存分析和ROC分析。通过ImmPort数据库分析，将免疫相关基因与F2RL1相关基因进行鉴定。使用GO、KEGG和GSEA进行功能富集分析。我们收集了参与者的宫颈细胞和血清，检测HPV和TCT，然后使用qPCR检测F2RL1 mRNA表达水平。我们还通过WB和ELISA技术验证了F2RL1蛋白的表达。我们的研究有一个惊人的发现——与正常组织相比，宫颈癌组织中F2RL1的表达水平显著升高，在不同病理类型中呈现出有趣的差异。此外，F2RL1高表达与总生存期（OS）、无进展间期（PFI）、无进展生存期（PFS）降低有关。F2RL1在ROC分析中表现出色，AUC为0.996。此外，F2RL1表达水平在不同的N分期、病理组织类型、治疗状态和种族群体中对宫颈癌有显著影响，这使我们能够建立一个预测模型。此外，我们鉴定了43个免疫相关基因。富集分析突出了它们与细胞运动和T细胞活化相关途径的关联。通过分析，我们发现F2RL1表达与大多数免疫细胞的浸润呈反比，尤其是TFH和细胞毒性细胞，这表明其与宫颈癌免疫逃逸可能存在联系。分子生物学实验也证实了宫颈脱落细胞和血清中F2RL1表达显著增加。我们的研究首次揭示了F2RL1在宫颈癌中的预测和早期检测意义及其与免疫浸润的相关性。F2RL1与宫颈癌的进展密切相关，可作为宫颈癌患者早期诊断和预后的生物标志物。
