Abstract
Background: RNA modification plays an important role in many diseases. A comprehensive study of tumor microenvironment (TME) characteristics mediated by RNA modification regulators will improve the understanding of TME immune regulation. Methods: We selected 26 RNA modification “writers” of lung adenocarcinoma (LUAD) samples and performed unsupervised clustering analysis to explore RNA modification patterns in LUAD. Differentially expressed genes (DEGs) with RNA modification patterns were screened to develop a “writers” of RNA modification score (WM score) system. The infiltration ratio of TME cell subsets was analyzed by CIBERSORT. Results: We identified two RNA modification modes showing different characteristics of overall survival (OS) and TME cell infiltration. According to WM score, LUAD patients were divided into a high-WM score group and a low-WM score group. High-scored patients had a poor prognosis and higher tumor mutation burden (TMB), they were more sensitive to four LUAD therapies (erlotinib, XA V939, gefitinib, and KU-55933) and more clinically responsive to PD-L1 treatment. Those with a low WM score showed higher stromal scores, ESTIMATE scores, and survival chance. Conclusion: Our work revealed the potential role of RNA modification patterns in TME, genetic variation, targeted inhibitor therapy, and immunotherapy. Identifying RNA modification pattern of LUAD patients help understand the characteristics of TME and may promote the development of immunotherapy strategies.
Highlights
The mortality of lung cancer far exceeds that resulting from breast cancer, pancreatic cancer, colon cancer, and prostate cancer (Siegel et al, 2018)
No significant statistical difference was found in the overall survival (OS) of Lung adenocarcinoma (LUAD) patients with or without these RNA modification “writer” mutations, suggesting that “writer” mutations may have a limited effect on the overall survival of LUAD patients (Figure 1B)
copy number variations (CNV) analysis showed that the amplification in copy number of adenosine deaminase acting on RNA (ADAR) and CPSF1 was the most extensive, while RBM15B, ZC3H13, ADARB2, and TRMT61A showed great CNV deletion, and no CNV occurred in KIAA1429 (Figure 1D)
Summary
The mortality of lung cancer far exceeds that resulting from breast cancer, pancreatic cancer, colon cancer, and prostate cancer (Siegel et al, 2018). LUAD accounts for almost half of all lung cancer deaths, with a 5-year survival rate as low as 15% (Kara et al, 2021; Spella and Stathopoulos, 2021). A-to-I editing consists of the irreversible conversion of adenosine to inosine catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes (Marceca et al, 2021). These RNA modification patterns participate in various physiological processes and play important regulatory roles in diseases including cancers, neurologic and metabolic diseases (Wilkinson et al, 2021). A comprehensive study of tumor microenvironment (TME) characteristics mediated by RNA modification regulators will improve the understanding of TME immune regulation
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