Li Yang, Zheng Ji-Na, Wang En-Hao, Gong Chan-Juan, Lan Keng-Fu, Ding XiaoJun
Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, China.
State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China.
PeerJ. 2020 Nov 26;8:e10385. doi: 10.7717/peerj.10385. eCollection 2020.
Increasing evidence has shown that N6-methyladenosine (m6A) RNA methylation regulators have important biological functions in human cancers. However, there are few studies on the value of m6A reader protein YTHDC2 in the diagnosis and tumor-infiltrating of head and neck squamous cell carcinoma (HNSCC). Therefore, it is important to understand the potential clinical value of YTHDC2 in the prognosis and immune infiltration of HNSCC.
In this study, gene expression profiles and the corresponding clinical information of 270 HNSCC patients were downloaded from the Gene Expression Omnibus (GEO) database. The gene co-expression network was established to verify whether YTHDC2 was related to the prognosis of HNSCC and verified again in the public database. The correlations between YTHDC2 and immune infiltration was investigated via Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA).
The results showed that YTHDC2 appeared in the blue module related to survival time and survival state and had a close correlation with the prognosis and immune infiltration level of HNSCC in public database. Patients with low expression of YTHDC2 had poor overall survival (OS) and recurrence-free survival (RFS) than those with high expression. In addition, the expression of YTHDC2 was positively correlated with the level of CD4+ T cell subpopulations infiltration in HNSCC.
Through this study, we found that YTHDC2 is a tumor suppressor gene with high expression in normal tissues and low expression in tumor tissues. In addition, YTHDC2 is correlated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells in HNSCC, which may become a potential marker for prognosis and immune infiltration of HNSCC.
越来越多的证据表明，N6-甲基腺苷（m6A）RNA甲基化调节剂在人类癌症中具有重要的生物学功能。然而，关于m6A阅读蛋白YTHDC2在头颈部鳞状细胞癌（HNSCC）诊断和肿瘤浸润方面的研究较少。因此，了解YTHDC2在HNSCC预后和免疫浸润中的潜在临床价值具有重要意义。
在本研究中，从基因表达综合数据库（GEO）下载了270例HNSCC患者的基因表达谱和相应的临床信息。建立基因共表达网络以验证YTHDC2是否与HNSCC的预后相关，并在公共数据库中再次进行验证。通过肿瘤免疫估计资源（TIMER）和基因表达谱交互式分析（GEPIA）研究YTHDC2与免疫浸润之间的相关性。
结果显示，YTHDC2出现在与生存时间和生存状态相关的蓝色模块中，并且在公共数据库中与HNSCC的预后和免疫浸润水平密切相关。YTHDC2低表达的患者比高表达的患者总生存期（OS）和无复发生存期（RFS）更差。此外，YTHDC2的表达与HNSCC中CD4+ T细胞亚群浸润水平呈正相关。
通过本研究，我们发现YTHDC2是一种在正常组织中高表达而在肿瘤组织中低表达的肿瘤抑制基因。此外，YTHDC2与HNSCC中B细胞、CD8+ T细胞、CD4+ T细胞、中性粒细胞和树突状细胞的免疫浸润水平相关，这可能成为HNSCC预后和免疫浸润的潜在标志物。
