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通过单细胞转录组学和多组学大数据分析揭示的宫颈癌中PTK6介导的免疫特征

PTK6 mediated immune signatures revealed by single cell transcriptomic and multi omics big data analysis in cervical cancer.

作者信息

Zhao Fen, Zhong Huanxin, You Lifang, Du Yi, Huang Changchang

机构信息

Department of Gynecology, First People's Hospital of Linping District, No. 369 Yingbin Road, Nanyuan Subdistrict, Linping District, Hangzhou, Zhejiang, China.

出版信息

Discov Oncol. 2025 Aug 16;16(1):1566. doi: 10.1007/s12672-025-03365-7.

DOI:10.1007/s12672-025-03365-7
PMID:40818002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12357816/
Abstract

BACKGROUND

Cervical cancer exhibits heterogeneous clinical outcomes, requiring improved prognostic tools. Single-cell RNA sequencing enables high-resolution analysis of tumor microenvironment cellular heterogeneity. This study developed a prognostic model for cervical cancer through single-cell transcriptomic analysis and immune infiltration characterization, focusing on PTK6 as a key biomarker.

METHODS

We analyzed TCGA and GEO transcriptomic data with single-cell RNA sequencing datasets. Fifteen machine learning algorithms constructed prognostic models using immune infiltration-related genes. Single-cell analysis employed Seurat for cell clustering and annotation. PTK6 expression was validated in H8 and HeLa cell lines via RT-qPCR and siRNA knockdown experiments.

RESULTS

Single-cell sequencing revealed distinct cellular populations including CD8T cells, CD4Tconv cells, and fibroblasts. The prognostic model achieved excellent performance with AUC values of 0.737-0.757 across 1-5 years. PTK6 showed significantly elevated expression in tumors and strong correlations with immune infiltration. Single-cell analysis confirmed PTK6 expression across multiple cell types. Functional validation demonstrated that PTK6 knockdown reduced HeLa cell proliferation, confirming its oncogenic role.

CONCLUSION

PTK6 emerges as a critical immune infiltration-related prognostic biomarker through single-cell transcriptomic analysis.

摘要

背景

宫颈癌表现出异质性的临床结果，需要改进预后工具。单细胞RNA测序能够对肿瘤微环境细胞异质性进行高分辨率分析。本研究通过单细胞转录组分析和免疫浸润特征分析，开发了一种针对宫颈癌的预后模型，重点关注PTK6作为关键生物标志物。

方法

我们使用单细胞RNA测序数据集分析了TCGA和GEO转录组数据。15种机器学习算法使用免疫浸润相关基因构建预后模型。单细胞分析采用Seurat进行细胞聚类和注释。通过RT-qPCR和siRNA敲低实验在H8和HeLa细胞系中验证PTK6表达。

结果

单细胞测序揭示了不同的细胞群体，包括CD8T细胞、CD4Tconv细胞和成纤维细胞。该预后模型在1至5年期间的AUC值为0.737 - 0.757，表现出色。PTK6在肿瘤中表达显著升高，且与免疫浸润密切相关。单细胞分析证实了PTK6在多种细胞类型中的表达。功能验证表明，PTK6敲低可降低HeLa细胞增殖，证实了其致癌作用。

结论

通过单细胞转录组分析，PTK6成为一种关键的免疫浸润相关预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4059/12357816/a7817947d22c/12672_2025_3365_Fig12_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4059/12357816/a17c1ea25719/12672_2025_3365_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4059/12357816/f3304a7145a4/12672_2025_3365_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4059/12357816/227d0ed6e33d/12672_2025_3365_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4059/12357816/8af0f86b1969/12672_2025_3365_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4059/12357816/b3054adc8ca4/12672_2025_3365_Fig11_HTML.jpg
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