N6-甲基腺苷 RNA 修饰（m6A）对 HPV 依赖性外阴鳞状细胞癌具有预后价值。
N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma.
机构信息
Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
出版信息
BMC Cancer. 2022 Sep 1;22(1):943. doi: 10.1186/s12885-022-10010-x.
BACKGROUND
Vulvar squamous cell carcinoma (VSCC) is an uncommon gynecologic malignancy but with an increasing incidence in recent years. Etiologically, VSCC is classified into two subtypes: HPV-dependent and HPV-independent. Localized VSCC is treated surgically and/or with radiation therapy, but for advanced, metastatic or recurrent disease, therapeutic options are still limited. N6-methyladenosine (m6A) is the most prevalent post-transcriptional messenger RNA (mRNA) modification and involved in many physiological processes. The group of m6A proteins can be further divided into: 'writers' (METTL3, METTL4, METTL14, WTAP, KIAA1429), 'erasers' (FTO, ALKBH5), and 'readers' (HNRNPA2B1, HNRNPC, YTHDC1, YTHDF1-3). Dysregulated m6A modification is implicated in carcinogenesis, progression, metastatic spread, and drug resistance across various cancer entities. Up to date, however, only little is known regarding the role of m6A in VSCC.
METHODS
Here, we comprehensively investigated protein expression levels of a diverse set of m6A writers, readers and erasers by applying immunohistochemical staining in 126 patients with primary VSCC.
RESULTS
In the entire study cohort, dominated by HPV-independent tumors, m6A protein expression was not associated with clinical outcome. However, we identified enhanced protein expression levels of the 'writers' METTL3, METTL14 and the 'reader' YTHDC1 as poor prognostic markers in the 23 patients with HPV-dependent VSCC.
CONCLUSION
Our study suggests dysregulated m6A modification in HPV-associated VSCC.
背景
外阴鳞状细胞癌（VSCC）是一种罕见的妇科恶性肿瘤，但近年来发病率呈上升趋势。从病因学上看，VSCC 分为 HPV 依赖性和 HPV 非依赖性两种亚型。局限性 VSCC 采用手术和/或放射治疗，但对于晚期、转移性或复发性疾病，治疗选择仍然有限。N6-甲基腺苷（m6A）是最常见的信使 RNA（mRNA）转录后修饰物，参与许多生理过程。m6A 蛋白组可进一步分为：“writers”（METTL3、METTL4、METTL14、WTAP、KIAA1429）、“erasers”（FTO、ALKBH5）和“readers”（HNRNPA2B1、HNRNPC、YTHDC1、YTHDF1-3）。m6A 修饰失调与多种癌症实体的致癌作用、进展、转移扩散和耐药性有关。然而，迄今为止，人们对 m6A 在 VSCC 中的作用知之甚少。
方法
我们通过免疫组织化学染色，对 126 例原发性 VSCC 患者进行了一组多样化的 m6A 书写者、读者和橡皮擦蛋白表达水平的综合研究。
结果
在整个研究队列中，以 HPV 非依赖性肿瘤为主，m6A 蛋白表达与临床结局无关。然而，我们发现，在 23 例 HPV 依赖性 VSCC 患者中，“writers”METTL3、METTL14 和“reader”YTHDC1 的蛋白表达水平升高与预后不良有关。
结论
我们的研究表明 HPV 相关 VSCC 中存在 m6A 修饰失调。
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