Department of Gynecology, The First Affiliated Hospital of Harbin Medical University, No. 23, postal street, Nangang District, Harbin City, PCODE:230100, Heilongjiang Province, China.
Department of Gynecological Oncology, Renji Hospital Affiliated To Medical College of Shanghai Jiaotong University, 160 Pujian Road, Pudong New Area, Shanghai, 310000, China.
Clin Transl Oncol. 2022 Jul;24(7):1413-1424. doi: 10.1007/s12094-022-02787-x. Epub 2022 Feb 27.
As an epigenetic regulation mechanism after transcription, RNA modification is installed by endogenous "writer" enzymes and is widely involved in a variety of physiological processes, including cancer progression. This study explored the RNA modification patterns of cervical cancer to clarify overall effect of RNA modification on tumor microenvironment (TME) characteristics and immune/targeted therapy.
26 RNA modification "writers" were clustered, and the RNA modification patterns and TME characteristics of cervical cancer patients in TCGA were systematically evaluated. Based on differentially expressed genes (DEGs) between different RNA modification patterns, an RNA modification "writer" score (WM score) system was developed to assess the RNA modification of a single sample.
Two different RNA modification patterns of cervical cancer were identified, and these patterns were significantly related to the prognosis and TME infiltration characteristics of patients. WM score was an independent risk factor for the prognosis of cervical cancer. High WM score was characterized by poor prognosis, low immune infiltration and low tumor mutation burden (TMB), while low-WM score was related to relatively long overall survival (OS), more immune components in TME and increased TMB. In addition, the low-WM score group was expected to be more sensitive to programmed cell death protein 1 (PD-1) therapy and showed lower predicted IC of chemotherapy drugs paclitaxel and cisplatin treatment.
This study identified and characterized RNA modification patterns, and clarified potential relationship between RNA modification patterns and immune infiltration characteristics and immunotherapy of cervical cancer, offering a new evaluation scheme for treatment of cervical cancer patients.
作为转录后的一种表观遗传调控机制，RNA 修饰由内源性“写入器”酶来安装，并广泛参与多种生理过程，包括癌症进展。本研究探索了宫颈癌的 RNA 修饰模式，以阐明 RNA 修饰对肿瘤微环境（TME）特征和免疫/靶向治疗的整体影响。
对 26 个 RNA 修饰“写入器”进行聚类，系统评估 TCGA 宫颈癌患者的 RNA 修饰模式和 TME 特征。基于不同 RNA 修饰模式之间的差异表达基因（DEGs），开发了 RNA 修饰“写入器”评分（WM 评分）系统，以评估单个样本的 RNA 修饰情况。
确定了两种不同的宫颈癌 RNA 修饰模式，这些模式与患者的预后和 TME 浸润特征显著相关。WM 评分是宫颈癌预后的独立危险因素。高 WM 评分的特征是预后不良、免疫浸润低和肿瘤突变负荷（TMB）低，而低 WM 评分与较长的总生存期（OS）、TME 中更多的免疫成分和增加的 TMB 相关。此外，低 WM 评分组预计对程序性细胞死亡蛋白 1（PD-1）治疗更敏感，并显示出较低的预测化疗药物紫杉醇和顺铂治疗的 IC。
本研究鉴定和描述了 RNA 修饰模式，并阐明了 RNA 修饰模式与宫颈癌免疫浸润特征和免疫治疗之间的潜在关系，为宫颈癌患者的治疗提供了一种新的评估方案。
