Hu Yuzhe, Li Yue, Jiang Chenfeng, Han Wenling, Chen Xiaohong, Wang Pingzhang, Xu Hongbo
Department of Immunology, NHC Key Laboratory of Medical Immunology (Peking University), Medicine Innovation Center for Fundamental Research on Major Immunology-related Diseases, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
J Cancer. 2025 Jul 24;16(11):3403-3414. doi: 10.7150/jca.110597. eCollection 2025.
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent malignancies with a poor prognosis. The underlying mechanisms driving HNSCC carcinogenesis are not fully elucidated. In this study, we identified dual specificity phosphatase 9 (DUSP9) as a carcinogenic factor in HNSCC development. According to the public data, DUSP9 was significantly up-regulated in HNSCC tumor tissues compared to normal tissues, confirmed by clinical data and single-cell RNA sequencing (scRNA-seq) data. Survival analysis revealed that high levels of DUSP9 expression contribute to poor prognosis in HNSCC patients. Knockdown of DUSP9 decreased, but overexpression of DUSP9 increased the proliferation and migration of HNSCC cells. ScRNA-seq data analysis suggested that DUSP9 was selectively expressed in tumor cells, with negligible expression in immune cells and stromal cells, and showed an elevated trend from primary tissues to metastatic tissues. Enrichment analyses of DUSP9-correlated genes suggested the involvement of DUSP9 in cell adhesion, wound healing, cell migration, transcription regulation and metabolic process. Furthermore, DUSP9 expression in tumor tissues exhibited an inverse relationship with immune cell infiltration within the tumor microenvironment (TME). In conclusion, this study provided evidence that DUSP9 was up-regulated in HNSCC tissues and may play a pivotal role in HNSCC progression, suggesting its potential as a novel biomarker.
头颈部鳞状细胞癌(HNSCC)是最常见的恶性肿瘤之一,预后较差。驱动HNSCC致癌作用的潜在机制尚未完全阐明。在本研究中,我们确定双特异性磷酸酶9(DUSP9)是HNSCC发生发展中的致癌因素。根据公开数据,与正常组织相比,DUSP9在HNSCC肿瘤组织中显著上调,临床数据和单细胞RNA测序(scRNA-seq)数据证实了这一点。生存分析显示,DUSP9的高表达水平导致HNSCC患者预后不良。敲低DUSP9会降低,但过表达DUSP9会增加HNSCC细胞的增殖和迁移。scRNA-seq数据分析表明,DUSP9在肿瘤细胞中选择性表达,在免疫细胞和基质细胞中的表达可忽略不计,并且从原发组织到转移组织呈现升高趋势。对DUSP9相关基因的富集分析表明,DUSP9参与细胞黏附、伤口愈合、细胞迁移、转录调控和代谢过程。此外,肿瘤组织中DUSP9的表达与肿瘤微环境(TME)内的免疫细胞浸润呈负相关。总之,本研究提供了证据表明DUSP9在HNSCC组织中上调,可能在HNSCC进展中起关键作用,提示其作为新型生物标志物的潜力。