WASF2 高甲基化：在头颈部鳞状细胞癌中的肿瘤抑制作用

Hypermethylated WASF2: tumor suppressive role in head and neck squamous cell carcinoma.

作者信息

Zhang Jianyun, Ding Zhuang, Chen Long, Qin Haiyan

机构信息

Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

Department of Dental Implantology and Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

出版信息

Transl Cancer Res. 2023 Jan 30;12(1):78-92. doi: 10.21037/tcr-22-1133. Epub 2022 Dec 31.

DOI:10.21037/tcr-22-1133

PMID:36760387

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9906064/

Abstract

BACKGROUND

WASF2 regulates actin reorganization during cell migration. WASF2 has been identified as a regulator of the development of gastric cancer, breast cancer, and pancreatic cancer. But its regulatory mechanisms remain unknown. Also, its function was absent in head and neck squamous cell carcinoma (HNSCC). Consequently, we examined the effect of DNA methylation on aberrant WASF2 expression in HNSCC.

METHODS

TNMplot, TIMER, GSEA pathway analysis, and the Kaplan-Meier Plotter database were used to analyze the expression, function, and prognostic value of WASF2, as well as the correlation between WASF2 and infiltrating immune cells in HNSCC or pan-cancer analysis. WASF2 promoter methylation levels and the correlation between WASF2 expression and WASF2 promoter methylation in HNSCC were evaluated using the DNMIVD database. The effect of DNA methylation inhibitor on WASF2 expression was demonstrated in the GEO database. Finally, the TISIDB database determined the relationships between WASF2 methylation, immune cell infiltration, and immune inhibitors.

RESULTS

WASF2 was significantly downregulated in HNSCC tissues where WASF2 promoter methylation was elevated. According to the GEO database, treatment with a DNA methylation inhibitor notably restored the mRNA expression of WASF2. WASF2 expression was also a favorable indicator of human papilloma virus (HPV)-positive HNSCC. Its level of promoter methylation had detrimental effects on patient survival. In addition, patients with elevated levels of WASF2 demonstrated active G2/M regulation, TGF-β signaling, Kras signaling, fatty acid metabolism, and p53 pathways. WASF2 was positively associated with tumor-killing immune cells, while WASF2 methylation was positively related to immunosuppressive cells and immune-inhibitors.

CONCLUSIONS

Hypermethylated WASF2 acted as a tumor suppressor of HNSCC by regulating tumor formation and immune imbalance.

摘要

背景

WASF2在细胞迁移过程中调节肌动蛋白重组。WASF2已被确定为胃癌、乳腺癌和胰腺癌发展的调节因子。但其调节机制仍不清楚。此外，它在头颈部鳞状细胞癌（HNSCC）中无功能。因此，我们研究了DNA甲基化对HNSCC中WASF2异常表达的影响。

方法

使用TNMplot、TIMER、GSEA通路分析和Kaplan-Meier Plotter数据库分析WASF2在HNSCC中的表达、功能和预后价值，以及WASF2与浸润免疫细胞之间的相关性或泛癌分析。使用DNMIVD数据库评估HNSCC中WASF2启动子甲基化水平以及WASF2表达与WASF2启动子甲基化之间的相关性。在GEO数据库中证明了DNA甲基化抑制剂对WASF2表达的影响。最后，TISIDB数据库确定了WASF2甲基化、免疫细胞浸润和免疫抑制剂之间的关系。

结果

在WASF2启动子甲基化升高的HNSCC组织中，WASF2显著下调。根据GEO数据库，用DNA甲基化抑制剂处理可显著恢复WASF2的mRNA表达。WASF2表达也是人乳头瘤病毒（HPV）阳性HNSCC的一个良好指标。其启动子甲基化水平对患者生存有不利影响。此外，WASF2水平升高的患者表现出活跃的G2/M调节、TGF-β信号传导、Kras信号传导、脂肪酸代谢和p53通路。WASF2与肿瘤杀伤免疫细胞呈正相关，而WASF2甲基化与免疫抑制细胞和免疫抑制剂呈正相关。