Epigenetic and Immune Profile Characteristics in Sinonasal Undifferentiated Carcinoma

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-11-20 DOI:10.1002/cam4.70413

Hyang Joo Ryu, Chung Lee, Sun Och Yoon

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Abstract

Introduction

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive malignancy originating in the nasal cavity and paranasal sinuses. Its pathogenesis and immune characteristics remain poorly understood.

Objectives

This study investigates the molecular aspects of SNUC, focusing on tumorigenesis and immunity.

Methods

For this purpose, spatial transcriptome analysis was employed to compare the gene expression profiles of SNUC tumor cells with those of normal epithelial cells, as well as to compare tumor-infiltrating immune cells with immune cells from normal, tumor-free tissue areas. For validation, next-generation sequencing tests and clinical sample studies were conducted.

Results

Spatial transcriptome analysis revealed notable upregulation of EZH2 and the histone family gene such as H3C2 (H3-clustered histone 2) in SNUC tumor cells. Additionally, gene set enrichment analysis identified significant activations in the histone deacetylase (HDAC) signaling pathway, histone acetyltransferase (HAT) pathway, polycomb repressive complex 2 (PRC2), and DNA methylation pathways. A notable decrease was observed in downregulated genes and pathways, including the mucin family of protein genes, the keratin protein gene, and the mucin glycosylation pathway. Next-generation sequencing did not reveal specific genetic mutations within these pathways, although mutations such as IDH2 R172S were noted. Clinical SNUC tissues confirmed increased immunoexpression of EZH2 and PRC2 markers. Analysis of tumor immunity revealed a characteristic immune cell signature, with a notable predominance of naïve B cells, macrophages, CD8 memory T cells, and Tregs in the SNUC microenvironment, alongside the increased expression of LAG3 in tumor-infiltrating immune cells.

Conclusion

Our study suggests epigenetic mechanisms, particularly via EZH2, play a crucial role in SNUC carcinogenesis. Furthermore, distinctive immune cell profiles in SNUC point to potential immune-related characteristics of this malignancy.

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鼻窦未分化癌的表观遗传学和免疫特征

导言鼻窦未分化癌（SNUC）是一种罕见的侵袭性极强的恶性肿瘤，起源于鼻腔和副鼻窦。人们对其发病机制和免疫特征仍然知之甚少。目的本研究探讨鼻腔分化癌的分子方面，重点是肿瘤发生和免疫。方法采用空间转录组分析比较 SNUC 肿瘤细胞与正常上皮细胞的基因表达谱，并比较肿瘤浸润免疫细胞与正常无肿瘤组织区域的免疫细胞。为了进行验证，还进行了新一代测序测试和临床样本研究。结果空间转录组分析显示，SNUC 肿瘤细胞中的 EZH2 和组蛋白家族基因如 H3C2（H3-簇组蛋白 2）明显上调。此外，基因组富集分析还发现组蛋白去乙酰化酶（HDAC）信号通路、组蛋白乙酰转移酶（HAT）通路、多聚核抑制复合体 2（PRC2）和 DNA 甲基化通路显著激活。观察到下调基因和通路明显减少，包括粘蛋白家族蛋白基因、角蛋白基因和粘蛋白糖基化通路。虽然发现了 IDH2 R172S 等基因突变，但下一代测序并未发现这些通路中存在特定的基因突变。临床SNUC组织证实EZH2和PRC2标记物的免疫表达增加。肿瘤免疫分析揭示了一种特征性的免疫细胞特征，在 SNUC 微环境中，幼稚 B 细胞、巨噬细胞、CD8 记忆 T 细胞和 Tregs 明显占优势，同时肿瘤浸润免疫细胞中 LAG3 的表达也有所增加。结论我们的研究表明，表观遗传机制（尤其是通过 EZH2）在 SNUC 癌变中起着至关重要的作用。此外，SNUC 中独特的免疫细胞特征表明这种恶性肿瘤具有潜在的免疫相关特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.