Yanjun Qu1, Hong Zhu2, Congcong Kong1, Xin Zheng3, Dejun Wang1, Xiuwei Chen4, Dandan Yuan5. 1. Department of Gynecology, The First Affiliated Hospital of Harbin Medical University, No. 23, postal street, Nangang District, Harbin City, PCODE:230100, Heilongjiang Province, China. 2. Department of Gynecological Oncology, Renji Hospital Affiliated To Medical College of Shanghai Jiaotong University, 160 Pujian Road, Pudong New Area, Shanghai, 310000, China. 3. Department of Gynecology, The First Hospital of Jiaxing, 1882 Zhonghuan South Road, Nanhu District, Jiaxing City, PCODE:330400, Zhejiang Province, China. 4. Department of Gynecology, The Third Affiliated Hospital of Harbin Medical University, No. 150, haping Road, health care road street, Nangang District, Harbin City, PCODE:230100, Heilongjiang Province, China. 5. Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, PCODE:230100, Heilongjiang Province, China. yuandandan_80@163.com.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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 IC50 of chemotherapy drugs paclitaxel and cisplatin treatment. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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 IC50 of chemotherapy drugs paclitaxel and cisplatin treatment. CONCLUSIONS: 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.
Authors: Thomas M Carlile; Nicole M Martinez; Cassandra Schaening; Amanda Su; Tristan A Bell; Boris Zinshteyn; Wendy V Gilbert Journal: Nat Chem Biol Date: 2019-09-02 Impact factor: 15.040