Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Naval Medical University, Naval Medical University, Shanghai 200003, P.R. China.
Department of Health Management Center, The First Affiliated Hospital of Naval Medical University, Shanghai 200438, P.R. China.
Aging (Albany NY). 2024 Jun 29;16(19):12781-12805. doi: 10.18632/aging.205981.
The AlkB homolog 7 (ALKBH7) is a nonheme iron (II) α-ketoglutarate-dependent dioxygenase superfamily member, which may affect the progression of several types of human cancer. However, the biological effect, especially the immune-related effect, of ALKBH7 in HNSC remains unclear. Herein, several databases were employed at first to assess the different expression of ALKBH7 as well as their relationship to the prognosis, RNA modification, DNA methylation modulation, immune microenvironment and chemotherapeutic responses of various types of cancers. We found that ALKBH7 was expressed differentially in pan-cancer, and correlated with a satisfied prognosis especially in HNSC. The expression of ALKBH7 was also associated with the level of immune cell infiltration, TMB, MSI, HRD, MMR deficiency, and DNA methyltransferases in a wide variety of cancers, which might be potentially related to the responses against chemotherapeutic agents. Next, the role of ALKBH7 in HNSC was further investigated. Western blot and immunohistochemical analysis in HNSC patients from the NMU cohort showed the reduced ALKBH7 expression level in tumor tissues. experiments of cell migration, invasion, and proliferation showed a potential protective effect of ALKBH7 in HNSC. Collectively, ALKBH7 might play a protective role in the development and progression of multiple cancers by affecting the metabolism and immune cell infiltration, especially HNSC, which could be a potential biomarker to predict prognosis and chemotherapeutic response.
ALKBH7 同源物 7（ALKBH7）是一种非血红素铁（II）α-酮戊二酸依赖性双加氧酶超家族成员，可能影响多种类型的人类癌症的进展。然而，ALKBH7 在头颈部鳞状细胞癌（HNSC）中的生物学效应，特别是免疫相关效应，尚不清楚。在此，首先利用多个数据库评估了 ALKBH7 的不同表达及其与各种癌症的预后、RNA 修饰、DNA 甲基化调节、免疫微环境和化疗反应的关系。我们发现，ALKBH7 在泛癌中表达不同，并且与满意的预后相关，尤其是在 HNSC 中。ALKBH7 的表达还与免疫细胞浸润水平、TMB、MSI、HRD、MMR 缺陷和各种癌症中的 DNA 甲基转移酶相关，这可能与对抗化疗药物的反应有关。接下来，进一步研究了 ALKBH7 在 HNSC 中的作用。NMU 队列中 HNSC 患者的 Western blot 和免疫组织化学分析显示肿瘤组织中 ALKBH7 的表达水平降低。细胞迁移、侵袭和增殖实验表明 ALKBH7 在 HNSC 中具有潜在的保护作用。总之，ALKBH7 通过影响代谢和免疫细胞浸润，可能在多种癌症的发生和发展中发挥保护作用，尤其是 HNSC，这可能是预测预后和化疗反应的潜在生物标志物。
