Zhang Beilei, Li Zhanghang, Yang Zhaojie, Yin Yidan, Duan Mingke, Wang Lei, Zhan Qirui, Wang Fu, An Ruifang
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.
BMC Cancer. 2025 Aug 5;25(1):1269. doi: 10.1186/s12885-025-14637-4.
Cervix cancer is a major health concern globally, being the fourth most prevalent type of cancer among females across the globe. Despite existing preventive measures like cytology and HPV testing, more precise diagnostic and treatment strategies are needed. This study leverages single-cell sequencing and transcriptome analysis to identify LLPS-linked therapeutic targets in cervical cancer. Utilizing data from the GEO database, we characterized six main cell types in cervical cancer and calculated LLPS scores for each. Analysis of LLPS-related genes revealed seven prognostic genes, and we constructed a predictive model demonstrating promising stability and accuracy. Furthermore, high-risk patients exhibited higher LLPS scores and lower survival probabilities, which may be influenced by differences in the tumor immune microenvironment, particularly involving immune cell types such as CD8 T cells, M0 macrophages and regulatory T cells. Exploring the expression patterns of model genes, we found PDIA6, PGK1, ASPH, and FNDC3B to be involved in immune infiltration during tumorigenesis. Finally, the signature genes that related to immune microenvironment was confirmed by immunohistochemistry staining. PGK1 was found to be most closely associated with the prognosis of cervical cancer. The correlation analysis of PGK1 with pathways in cervical cancer revealed that the expression level of PGK1 is associated with lipid peroxidation. Furthermore, our analysis using immunofluorescence and flow cytometry showed that lipid peroxidation increased after PGK1 knockdown. We further employed the proliferation experiment and cell-derived xenograft (CDX) mouse model to verify that downregulating PGK1 suppresses proliferation of cervical cancer in vitro and in vivo. Taken together, our study provides comprehensive insights into cervical cancer prognosis, identifying PGK1 as a potential therapeutic target among LLPS-related genes.
The online version contains supplementary material available at 10.1186/s12885-025-14637-4.
宫颈癌是全球主要的健康问题，是全球女性中第四大常见癌症类型。尽管存在细胞学和HPV检测等现有预防措施，但仍需要更精确的诊断和治疗策略。本研究利用单细胞测序和转录组分析来确定宫颈癌中与液-液相分离（LLPS）相关的治疗靶点。利用来自GEO数据库的数据，我们对宫颈癌中的六种主要细胞类型进行了表征，并计算了每种细胞类型的LLPS评分。对LLPS相关基因的分析揭示了七个预后基因，我们构建了一个预测模型，显示出良好的稳定性和准确性。此外，高危患者表现出更高的LLPS评分和更低的生存概率，这可能受肿瘤免疫微环境差异的影响，特别是涉及CD8 T细胞、M0巨噬细胞和调节性T细胞等免疫细胞类型。通过探索模型基因的表达模式，我们发现PDIA6、PGK1、ASPH和FNDC3B参与肿瘤发生过程中的免疫浸润。最后，通过免疫组织化学染色证实了与免疫微环境相关的特征基因。发现PGK1与宫颈癌的预后关系最为密切。PGK1与宫颈癌相关通路的相关性分析表明，PGK1的表达水平与脂质过氧化有关。此外，我们使用免疫荧光和流式细胞术的分析表明，PGK1敲低后脂质过氧化增加。我们进一步采用增殖实验和细胞衍生异种移植（CDX）小鼠模型来验证下调PGK1在体外和体内均可抑制宫颈癌的增殖。综上所述，我们的研究为宫颈癌预后提供了全面的见解，确定PGK1是LLPS相关基因中的一个潜在治疗靶点。
在线版本包含可在10.1186/s12885-025-14637-4获取的补充材料。
