RNA modification "writer"-mediated RNA modification patterns and tumor microenvironment characteristics of cervical cancer

Clin Transl Oncol. 2022 Jul;24(7):1413-1424. doi: 10.1007/s12094-022-02787-x. Epub 2022 Feb 27.

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.

Keywords: Cervical cancer; Immunotherapy; RNA modification “writers”; Tumor microenvironment; WM score.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Epigenesis, Genetic
  • Female
  • Humans
  • Prognosis
  • RNA / genetics
  • Tumor Microenvironment* / genetics
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / therapy

Substances

  • Biomarkers, Tumor
  • RNA