Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Zhengzhou University, 2nd, Jingba RoadHenan Province, Zhengzhou, 450053, China.
J Transl Med. 2022 Sep 4;20(1):385. doi: 10.1186/s12967-022-03600-7.
Cervical cancer is the fourth most common cancer in women. N-dimethyladenosine (mA) mRNA methylation is closely associated with cervical cancer.
Using TCGA database, we studied the expression and mutation of mA-related genes in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and obtained genetic characteristics based on an mA risk model and prognostic value of mA. We studied the effects of the mA risk score on immune features and genomic changes of patients with CESC, evaluated the sensitivity of patients with CESC to different small-molecule drugs based on the mA risk score, and established a clinical prediction model.
Ten mA-related genes were differentially expressed between CESC and normal tissues. High-risk patients had a low overall survival (OS) and significantly low immune scores but showed no significantly altered stromal scores. The tumor mutation burden (TMB) and tumor neoantigen levels significantly differed between the high- and low-risk groups. In the high-risk group, copy number variation (CNV) changes mainly led to gene amplification, while in the low-risk group, CNV changes primarily manifested as gene copy number deletions. ZC3H13 expression was low in CESC tissues. ZC3H13 knockdown promoted CESC cell proliferation, migration, and invasion, reducing the RNA methylation levels. Rapamycin suppressed the CESC cell proliferation, migration, and invasion abilities, increasing the mA levels.
mA mRNA methylation is closely related to the occurrence, development, immune invasion, drug sensitivity, and prognosis of cervical cancer. The prognostic mA feature model of mA signature genes can accurately predict the OS of patients with CESC. Drugs targeting factors regulating mA mRNA methylation might offer a good prospect for treating cervical cancer.
宫颈癌是女性中第四常见的癌症。N6-二甲基腺苷（mA）mRNA 甲基化与宫颈癌密切相关。
我们使用 TCGA 数据库研究了 mA 相关基因在宫颈鳞状细胞癌和宫颈内膜腺癌（CESC）中的表达和突变，并基于 mA 风险模型和 mA 的预后价值获得了遗传特征。我们研究了 mA 风险评分对 CESC 患者免疫特征和基因组变化的影响，基于 mA 风险评分评估了 CESC 患者对不同小分子药物的敏感性，并建立了临床预测模型。
10 个 mA 相关基因在 CESC 和正常组织之间存在差异表达。高风险患者的总生存期（OS）较低，免疫评分显著较低，但基质评分无明显改变。肿瘤突变负荷（TMB）和肿瘤新生抗原水平在高风险组和低风险组之间存在显著差异。在高风险组中，拷贝数变异（CNV）变化主要导致基因扩增，而在低风险组中，CNV 变化主要表现为基因拷贝数缺失。ZC3H13 在 CESC 组织中表达较低。ZC3H13 敲低促进 CESC 细胞增殖、迁移和侵袭，降低 RNA 甲基化水平。雷帕霉素抑制 CESC 细胞增殖、迁移和侵袭能力，增加 mA 水平。
mA mRNA 甲基化与宫颈癌的发生、发展、免疫浸润、药物敏感性和预后密切相关。mA 特征基因的预后 mA 特征模型可以准确预测 CESC 患者的 OS。针对调节 mA mRNA 甲基化的因素的药物可能为治疗宫颈癌提供良好的前景。
