Abstract
The aim of this study was to elucidate the correlation between m6A modification and the tumor immune microenvironment (TIME) in prostate cancer (PCa) and to identify the m6A regulation patterns suitable for immune checkpoint inhibitors (ICIs) therapy. We evaluated the m6A regulation patterns of PCa based on 24 m6A regulators and correlated these modification patterns with TIME characteristics. Three distinct m6A regulation patterns were determined in PCa. The m6A regulators cluster with the best prognosis had significantly increased METTL14 and ZC3H13 expression and was characterized by low mutation rate, tumor heterogeneity, and neoantigens. The m6A regulators cluster with a poor prognosis had markedly high KIAA1429 and HNRNPA2B1 expression and was characterized by high intratumor heterogeneity and Th2 cell infiltration, while low Th17 cell infiltration and Macrophages M1/M2. The m6Ascore was constructed to quantify the m6A modification pattern of individual PCa patients based on m6A-associated genes. We found that the low-m6Ascore group with poor prognosis had a higher immunotherapeutic response rate than the high-m6Ascore group. The low-m6Ascore group was more likely to benefit from ICIs therapy. This study was determined that immunotherapy is more effective in low-m6Ascore PCa patients with poor prognosis.
Highlights
Prostate cancer (PCa) is a serious threat to men around the world with mortality that is second only to lung cancer [1, 2]
The frequency of mutations of m6A regulators was near the bottom (Figure 1D), which showed no link with tumor development
Based on the relationship between m6A modification and immune cell infiltration in prostate cancer (PCa), we further investigated m6A Modification and Efficacy of immune checkpoint inhibitors (ICIs) for PCa whether m6A modification is related to the effect of tumor immunotherapy
Summary
Prostate cancer (PCa) is a serious threat to men around the world with mortality that is second only to lung cancer [1, 2]. Radical surgery and radiation therapy are effective treatment methods for early PCa. Many people lack awareness of the need for PCa screening. Most patients are in advanced or late metastasis stages at the time of diagnosis. Endocrine therapy has become the preferred treatment. PCa is likely to enter the drug-resistant stage from the hormone-sensitive stage after approximately 18 months of endocrine therapy. Marked advances have been made in the field of tumor treatment by immune checkpoint inhibitors (ICIs). Recent phase II clinical trials (NCT02601014, NCT02787005) revealed that ICIs are only effective for certain patients, and the disease control rate does not exceed 20% in PCa [3, 4]. Improving the defects of ICIs to increase their clinical efficacy is an urgent problem to be solved
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