空间转录组学分析显示hpv依赖型和非hpv依赖型外阴鳞状细胞癌的肿瘤微环境存在显著差异。

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-02-01 DOI:10.1016/j.ygyno.2025.01.002

Hasan B. Mirza , Ashton Hunt , Darren P. Ennis , Jacqueline McDermott , Iain A. McNeish

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引用次数: 0

摘要

目的：外阴鳞状细胞癌（VSCC）可分为hpv依赖型（HPVd）或hpv非依赖型（HPVi）。hpv VSCC通常发生在年轻女性，预后较好，由高级别鳞状上皮内病变（HSIL）发展而来。hpv VSCC主要影响老年妇女，发生在慢性炎症区域，特别是地衣硬化（LS）。我们利用基于测序的空间转录组学来探索hpv和hpv VSCC患者队列中的基因表达。方法：使用10x Genomics Visium空间转录组学平台分析4例早期VSCC（2例hpv， 2例hpv）不同区域（SCC，炎症，LS， HSIL）的基因表达。使用CIBERSORTx推断细胞特异性类型表达。结果：共检出Visium斑点28183个；每个都包含大约20-50个细胞。每个点的读数从9903到68,527不等。hpv （N = 601）比hpv （N = 72）有更多的基因上调，且不同病因间角蛋白和胶原蛋白基因差异显著。无论病因如何，SCC和邻近炎症区域的基因表达惊人地相似。IL-17信号在HPVd样品中上调。令人惊讶的是，CIBERSORTx推断hpv组织中的CD45+细胞明显多于hpv组织，特别是CD4+静息记忆细胞和SCC区域的滤泡辅助T细胞。免疫细胞从侵袭前组织的静息状态转移到鳞状细胞癌和肿瘤周围炎症区域的激活状态。结论：本研究是空间转录组学在VSCC中的首次应用，在hpv SCC中发现的免疫细胞明显多于hpv SCC。这些数据将作为未来研究的基础。

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Spatial transcriptomic analysis reveals significant differences in tumor microenvironment in HPV-dependent and HPV-independent vulvar squamous cell carcinoma

Objective

Vulvar squamous cell carcinoma (VSCC) can be either HPV-dependent (HPVd) or HPV-independent (HPVi). HPVd VSCC typically occurs in younger women, has a more favorable prognosis, and develops from high-grade squamous intraepithelial lesions (HSIL). HPVi VSCC predominantly affects older women and arises within areas of chronic inflammation, particularly lichen sclerosis (LS). We utilized sequencing-based spatial transcriptomics to explore gene expression in a cohort of patients with HPVi and HPVd VSCC.

Methods

We analysed gene expression in distinct areas (SCC, inflammation, LS, HSIL) from four early-stage VSCC cases (two HPVi, two HPVd) using the 10× Genomics Visium spatial transcriptomics platform. Cell-specific type expression was inferred using CIBERSORTx.

Results

28,183 Visium spots were detected; each contained an estimated 20–50 cells. Reads per spot ranged from 9903 to 68,527. More genes were upregulated in HPVd (N = 601) than HPVi (N = 72) with distinct differences in Keratin and Collagen genes between etiologies. Gene expression was strikingly similar between SCC and adjacent inflammatory areas, regardless of etiology. IL-17 signaling was upregulated in HPVd samples. Surprisingly, CIBERSORTx inferred significantly more CD45+ cells in HPVi tissues than HPVd, especially CD4+ resting memory and follicular helper T cells in SCC areas. Immune cells moved from resting states in the pre-invasive tissues to activated states in the SCC and peri-tumoral inflammatory areas.

Conclusions

This study represents the first application of spatial transcriptomics in VSCC, with significantly more immune cells identified in HPVi SCC than in HPVd SCC. These data will act as a baseline for future studies.

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy