Poster Presentation 45th Lorne Genome Conference 2024

Pan-cancer analysis links altered RNA m7G methyltransferase expression to oncogenic pathways, immune cell infiltration and overall survival (#169)

Anni Su 1 , Renhua Song 1 , Justin Wong 1
  1. Epigenetics and RNA Biology Laboratory, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia

Background: N7-methylguanosine (m7G) modification is one of the most prevalent RNA modifications in humans. Dysregulated m7G modification caused by aberrant expression of m7G writers (METTL1, WDR4, RNMT, FAM103A1, WBSCR22 and TRMT112) contributes to cancer development. However, the comprehensive investigation of m7G writers in the pan-cancer cohort is limited. This study aims to systematically investigate the molecular alteration and clinical relevance of m7G methyltransferase in human cancers. 

Methods: We conducted an analysis of gene expression, genetic alterations, and clinical data from 33 cancer types downloaded from the TCGA database. Kaplan–Meier analysis assessed the correlation between the m7G writers and patient survival across 33 cancer types. Gene set variation analysis and Pearson correlation tests determined associations between m7G writers and cancer-related hallmark pathways. We derived m7G scores using PCA algorithms based on the expression of the m7G writers. m7G score was used to determine the association of m7G writers and immune cell infiltration in tumours.

Results: Copy number alterations in m7G writers were infrequent in most cancer types, except for METTL1, which showed frequent amplification in glioblastoma and sarcoma. Dysregulated expression of m7G writers was observed across 18 types of human cancer, suggesting their roles in tumorigenesis. High expression of m7G writers correlated with overall survival in cancer patients, notably in kidney renal clear cell carcinoma (KIRC). Additionally, the expression of m7G writer is correlated with the activation or inhibition of cancer-related hallmark pathways. Furthermore, lower m7G scores correlated with increased immune cell infiltration in the KIRC tumour.

Conclusion: Our study highlights genetic alterations, expression patterns and clinical relevance of m7G writers across various cancers. Overall, this study provides a resource to infer the role of m7G writers in cancer and provides insights into the role of m7G writers as cancer biomarkers and therapeutic targets