Gu Zongting, Du Yongxing, Zhao Xueping, Wang Chengfeng
Department of Abdominal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
School of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, Shenyang, China.
Front Cell Dev Biol. 2022 Feb 9;10:822011. doi: 10.3389/fcell.2022.822011. eCollection 2022.
Hepatocellular carcinoma (HCC) has poor prognosis and is usually diagnosed only at an advanced stage. Identification of novel biomarkers is critical to early diagnosis and better prognosis for HCC patients. N6-methyladenosine (mA) RNA methylation regulators play important roles in the development of many tumors. However, the mA writer complex, a key executor of mA methylation modification, has not been independently investigated, and its specific bioinformatics analysis has not yet been performed in HCC. In this study, we used multiple public databases to evaluate the diagnostic, therapeutic, and prognostic value of the mA writers in HCC. The results showed that expression levels of METTL3, VIRMA and CBLL1 were significantly increased, while expression levels of METTL14 and ZC3H13 were significantly decreased in HCC, which was closely related to clinicopathological factors, such as tumor stage and prognosis. Bioinformatics further explored the possible underlying mechanisms by which the mA writer complex are involved in activation of tumor-promoting pathways and/or inhibition of tumor-suppressing pathways, including apoptosis, cell cycle, DNA damage response and EMT. Furthermore, we showed that the mA writer complex is correlated with immune cell infiltration and immunoregulator expression in HCC. In conclusion, the mA writer complex may represent a promising biomarker and target that can guide targeted therapy or immunotherapy for HCC patients.
肝细胞癌（HCC）预后较差，通常仅在晚期才被诊断出来。识别新型生物标志物对于HCC患者的早期诊断和改善预后至关重要。N6-甲基腺苷（m⁶A）RNA甲基化调节剂在许多肿瘤的发生发展中起重要作用。然而，m⁶A甲基化修饰的关键执行者——m⁶A书写复合体尚未被单独研究，其在HCC中的具体生物信息学分析也尚未进行。在本研究中，我们使用多个公共数据库评估m⁶A书写蛋白在HCC中的诊断、治疗和预后价值。结果显示，HCC中METTL3、VIRMA和CBLL1的表达水平显著升高，而METTL14和ZC3H13的表达水平显著降低，这与肿瘤分期和预后等临床病理因素密切相关。生物信息学进一步探究了m⁶A书写复合体参与激活促肿瘤通路和/或抑制抑肿瘤通路的潜在机制，包括细胞凋亡、细胞周期、DNA损伤反应和上皮-间质转化。此外，我们发现m⁶A书写复合体与HCC中的免疫细胞浸润和免疫调节因子表达相关。总之，m⁶A书写复合体可能是一种有前景的生物标志物和靶点，可指导HCC患者的靶向治疗或免疫治疗。
