Integrative analysis of ASXL family genes reveals ASXL2 as an immunoregulatory molecule in head and neck squamous cell carcinoma

被引：0
作者：
Liu, Qian [1 ,2 ,3 ]
Zhu, Wenhao [3 ,6 ]
Tang, Chenpeng [1 ,2 ,3 ]
Liu, Wenbin [4 ]
Luo, Xiangjian [1 ,2 ,3 ,5 ]
机构：
[1] Cent South Univ, Hunan Canc Hosp, Xiangya Sch Med, Hunan Key Lab Oncotarget Gene, Changsha 410013, Hunan, Peoples R China
[2] Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China
[3] Cent South Univ, Canc Res Inst, Key Lab Carcinogenesis & Canc Invas, Chinese Minist Educ,Sch Basic Med, Changsha 410078, Hunan, Peoples R China
[4] Cent South Univ, Hunan Canc Hosp, Dept Pathol, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China
[5] Cent South Univ, Key Lab Biol Nanotechnol, Natl Hlth Commiss, Changsha 410078, Hunan, Peoples R China
[6] Cent South Univ, Xiangya Hosp, Disorders Prostate Canc Multidisciplinary Team, Dept Urol,Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China
来源：
SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Head and neck squamous cell carcinoma; ASXL2; Prognosis; Immunotherapy; Immunoregulation; RECIPROCAL REGULATION; CANCER GENOMICS; RECURRENT; PROLIFERATION; CHEMOTHERAPY; EXPRESSION; DATABASE; ALPHA; SEX;
D O I：
10.1038/s41598-024-82815-8
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Despite the progress in conventional treatments for head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate remains below 70%. Enhancing immunotherapy outcomes through personalized treatment strategies, particularly by identifying immune-related biomarkers, is critical. The ASXL family are associated with malignancies, but their relationship with HNSCC has not been elucidated. In this study, we found that high expression of ASXL2 is associated with better prognosis in HNSCC patients. Analysis revealed a significant positive correlation between ASXL2 and immune infiltration. Functional analysis suggests that ASXL2 co-expressed genes in HNSCC patients are enriched in the JAK-STAT signaling pathway, and patients with high expression show an even greater enrichment in T cell and B cell receptor signaling pathways. Utilizing the NPC single-cell dataset, ASXL2's widespread expression in the tumor microenvironment was confirmed, and its co-expressed genes were found to be highly associated with immune cell function. Experimental validation showed a correlation between ASXL2 expression and T cell secretion of interferon-gamma (IFN gamma), confirming that high ASXL2 expression facilitates T cell activation. Overall, our findings underscore the important role of ASXL2 in immune activation, suggesting its potential as a promising biomarker for tailoring immunotherapy strategies in HNSCC patients.
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页数：14
相关论文
共 63 条
[1]  
Mody M.D., Rocco J.W., Yom S.S., Haddad R.I., Saba N.F., Head and neck cancer, Lancet, 398, pp. 2289-2299, (2021)
[2]  
Johnson D.E., Et al., Head and neck squamous cell carcinoma, Nat. Rev. Dis. Prim, 6, (2020)
[3]  
Haddad R.I., Shin D.M., Recent advances in head and neck cancer, N Engl. J. Med, 359, pp. 1143-1154, (2008)
[4]  
Ferris R.L., Et al., Nivolumab for recurrent squamous-cell carcinoma of the head and neck, N. Engl. J. Med, 375, pp. 1856-1867, (2016)
[5]  
Bhat A.A., Tumor microenvironment: An evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy, Signal. Transduct. Target. Ther., 6, (2021)
[6]  
Liao C., Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma, J. Exp. Clin. Cancer Res., 42, (2023)
[7]  
Chen Y.P., Et al., Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy, Ann. Oncol, 30, pp. 68-75, (2019)
[8]  
Jia S., Et al., Unlocking the potential: Targeting metabolic pathways in the tumor microenvironment for cancer therapy, Biochim. Biophys. Acta, 1879, (2024)
[9]  
Chen J., Colorectal cancer: Metabolic interactions reshape the tumor microenvironment, Biochim Biophys. Acta, 1877, 5
[10]  
Katoh M., Functional and cancer genomics of ASXL family members, Br. J. Cancer, 109, pp. 299-306, (2013)
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