Integrating Single-Cell RNA-Seq and Bulk RNA-Seq to Construct a Novel γδT Cell-Related Prognostic Signature for Human Papillomavirus-Infected Cervical Cancer - Cancer Control Volume 31 - Article

Sep 21, 2026

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Gamma delta (γδ) T cells show dual functions in tumors, yet their specific contribution to HPV-infected cervical cancer prognosis remains unclear. This study integrates single-cell RNA-seq and bulk RNA-seq with clinical data to define γδT cell-related prognostic signatures in the cervical tumor microenvironment. scRNA-seq and trajectory analyses characterize HPV-dependent γδT cell heterogeneity, while hdWGCNA and machine learning identify key gene modules. RT-qPCR validates hub genes, yielding an eight-gene signature that supports independent survival prediction.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

HPV and cervical cancer overview

γδT cells in tumors

Integrating Single-Cell RNA-Seq and Bulk RNA-Seq to Construct a Novel γδT Cell-Related Prognostic Signature for Human Papillomavirus-Infected Cervical Cancer Cancer Control Volume 31: 1–15 © The Author(s) 2024 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions) [DOI: 10.1177/10732748241274228](DOI: 10.1177/10732748241274228)[ ](DOI: 10.1177/10732748241274228)[journals.sagepub.com/home/ccx](journals.sagepub.com/home/ccx) Xiaochuan Wang, MM 1,*, Yichao Jin, MD 1,*, Liangheng Xu, MM 1, Sizhen Tao, MM 1, Yifei Wu, MM 1, and Chunping Ao, MD 1 􀀁 Abstract Background: Gamma delta (γδ) T cells play dual roles in human tumors, with both antitumor and tumor-promoting functions. However, the role of γδT cells in HPV-infected cervical cancer is still undetermined. Therefore, we aimed to identify γδT cellrelated prognostic signatures in the cervical tumor microenvironment. Methods: Single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data, and corresponding clinical information of cervical cancer patients were obtained from the TCGA and GEO databases. The Seurat R package was used for single-cell analysis, and machine learning algorithms were used to screen and construct a γδT cell-related prognostic signature. Real-time quantitative PCR (RT-qPCR) was performed to detect the expression of prognostic signature genes. Results: Single-cell analysis indicated distinct populations of γδT cells between HPV-positive (HPV+) and HPV-negative (HPV-) cervical cancers. A trajectory analysis indicated γδT cells clustered into differential clusters with the pseudotime. High-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) identiﬁed the key γδT cell-related gene modules. Bulk RNA-seq analysis also demonstrated the heterogeneity of immune cells, and the γδT-score was positively associated with inﬂammatory response and negatively associated with MYC stemness. Eight γδT cell-related hub genes (GTRGs), including ITGAE, IKZF3, LSP1, NEDD9, CLEC2D, RBPJ, TRBC2, and OXNAD1, were selected and validated as a prognostic signature for cervical cancer. Conclusion: We identiﬁed γδT cell-related prognostic signatures that can be considered independent factors for survival prediction in cervical cancer. Keywords cervical cancer, γδT cells, prognostic signature, immune cell inﬁltration, nomogram Received April 26, 2024. Received revised June 11, 2024. Accepted for publication July 17, 2024. 1 Department of Dermatology, The First People’s Hospital of Yunnan Province, the Afﬁliated Hospital of Kunming University of Science and Technology, Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, China *These authors contributed equally to this work. Corresponding Authors: Chunping Ao, Department of Dermatology, The First People’s Hospital of Yunnan Province, Yunnan Provincial Key Laboratory of Clinical Virology, 157 Jinbi Road, Kunming 650032, China. Email: [1209993635@qq.com](1209993635@qq.com) Yifei Wu, Department of Dermatology, The First People’s Hospital of Yunnan Province, Yunnan Provincial Key Laboratory of Clinical Virology, 157 Jinbi Road, Kunming 650032, China. Email: [kmwyf006@163.com](kmwyf006@163.com) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as speciﬁed on the SAGE and Open Access pages ([https://us.sagepub.com/en-us/nam/open-access-at-sage](https://us.sagepub.com/en-us/nam/open-access-at-sage)). Data Availability Statement included at the end of the article Introduction Human papillomavirus (HPV) is a small-double-stranded circular DNAvirus with a tropism for squamous epithelium and hasid

FAQs

What gap does the study address about γδT cells in cervical cancer?

Although γδT cells can act as antitumor or tumor-promoting cells, their role in prognosis for HPV-infected cervical cancer had not been clearly determined. The study aims to identify γδT cell-related prognostic signatures in this setting.

How were single-cell and bulk RNA-seq data used?

Single-cell RNA-seq data were analyzed with Seurat and trajectory/pseudotime approaches to assess γδT cell populations in HPV-positive versus HPV-negative tumors. Bulk RNA-seq was used to evaluate immune cell heterogeneity and compute a γδT score.

What is the prognostic signature and how was it validated?

The study selected eight γδT cell-related hub genes (GTRGs)—ITGAE, IKZF3, LSP1, NEDD9, CLEC2D, RBPJ, TRBC2, and OXNAD1—as a prognostic signature. RT-qPCR was performed to validate expression of these signature genes.

Sep 21, 2026

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