中国口腔颌面外科杂志

中国口腔颌面外科杂志 ›› 2025, Vol. 23 ›› Issue (3): 236-243.doi: 10.19438/j.cjoms.2025.03.005

• 论著 • 上一篇    下一篇

HPV相关性与非HPV相关性头颈癌细胞组成和分子表型的差异探讨

薛鹏鑫, 孙露露#, 孙树洋#   

  1. 上海交通大学医学院附属第九人民医院 口腔颌面-头颈肿瘤科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011
  • 收稿日期:2025-01-17 修回日期:2025-03-07 出版日期:2025-05-20 发布日期:2025-06-05
  • 通讯作者: 孙树洋,E-mail: sunshuyang@sjtu.edu.cn;孙露露,E-mail: lulusun222@163.com。#共同通信作者
  • 作者简介:薛鹏鑫（1999-）,男,硕士研究生,E-mail: xpx991115@sjtu.edu.cn
  • 基金资助:
    国家自然科学基金重点项目（82030085）;上海市重中之重研究项目（2022ZZ01017）

Differences in cellular composition and molecular phenotype between HPV-related and non-HPV-related head and neck cancers

Xue Pengxin, Sun Lulu, Sun Shuyang   

  1. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology. Shanghai 200011, China
  • Received:2025-01-17 Revised:2025-03-07 Online:2025-05-20 Published:2025-06-05

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摘要： 目的：探讨人乳头瘤病毒（human papillomavirus, HPV）相关性（HPV+）与非HPV相关性（HPV-）头颈癌的肿瘤微环境和分子表型的差异。方法：基于cbioportal等开放式分析平台获得癌症基因组图谱（The Cancer Genome Atlas, TCGA）公共数据库中头颈癌基因组、转录组和蛋白质组学测序数据,根据患者HPV感染状态分为HPV+和HPV-两组。首先基于转录组数据使用CIBERSORTx细胞分型矩阵推测HPV+与HPV-头颈癌的细胞组成差异;其次通过基因组、转录组和蛋白质组学测序数据,分别分析HPV+头颈癌相较于HPV-头颈癌中突变频率更高的基因、显著富集的通路和显著高表达的蛋白。结果：HPV+头颈癌在以下几方面与HPV-头颈癌存在显著差异。①细胞组分—B细胞、CD4+ T细胞、树突状细胞浸润比例显著提升。②分子表型—CCM2L、CBFA2T2、NECAB3等基因突变频率显著增加;神经活性配体-受体相互作用通路显著富集,CLDN7、SYK等蛋白表达水平高。③FADS1及ELF3潜在参与或调控HPV+头颈癌的上述表型演变。FADS1是HPV16 E2的潜在互作蛋白,而ELF3是HPV+上皮特异性表达的转录因子,两者均与神经活性配体-受体相互作用通路基因集合呈显著正相关。结论：相比HPV-头颈癌,HPV+头颈癌中的微环境细胞亚型分布及潜在调控元件显著不同,体现为免疫细胞比例更高,且富集神经信号传导和免疫应答等通路。

关键词: 头颈癌, 人乳头瘤病毒, 肿瘤微环境, 遗传学改变, 神经相关通路

Abstract: PURPOSE: To investigate the differences in tumor microenvironment and molecular phenotype between human papillomavirus (HPV)-related (HPV+) and non-HPV-related (HPV-) head and neck cancers (HNC). METHODS: Genomic, transcriptomic, and proteomic sequencing data for HNC were obtained from the TCGA public database via open-access platforms such as cbioportal. The patients were categorized into HPV+ and HPV- group based on HPV infection status. First, the CIBERSORTx cell-type deconvolution algorithm was applied to transcriptomic data to estimate differences in cellular composition between HPV+ and HPV- HNC. Subsequently, genomic, transcriptomic, and proteomic data were analyzed to identify genes with significantly increased mutation frequencies, enriched pathways, and upregulated proteins in HPV+ HNC compared to HPV- HNC. RESULTS: Significant differences were observed between HPV+ and HPV- HNC. ①Cellular composition: HPV+ tumors exhibited significantly higher infiltration of B cells, CD4+ T cells, and dendritic cells. ②Multi-omics alterations: genes such as CCM2L, CBFA2T2, and NECAB3 showed higher mutation frequencies in HPV+ tumors. The neuroactive ligand-receptor interaction pathway was significantly enriched in HPV+ tumors, proteins such as CLDN7 and SYK displayed higher expression levels in HPV+ tumors. ③FADS1 and ELF3 potentially participated in or regulated the phenotypic evolution of HPV+ HNC. FADS1 was a potential interacting protein of HPV16 E2, while ELF3 was a transcription factor specifically expressed in HPV+ epithelial tissues. Both genes exhibited a significant positive correlation with the gene set associated with the neuroactive ligand-receptor interaction pathway. CONCLUSIONS: Compared to HPV- HNC, the distribution of microenvironmental cell subtypes and potential regulatory elements in HPV+ HNC is significantly different, characterized by a higher proportion of immune cells and enrichment in pathways related to neural signaling and immune response.

Key words: Head and neck cancer, Human papillomavirus, Tumor microenvironment, Genetic alterations, Neuro-related pathways

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