m6A Methylation Regulators Are Predictive Biomarkers for Tumour Metastasis in Prostate Cancer

Abstract

Prostate cancer (PCa) is one of the most common cancers in men. Usually, most PCas at initial diagnosis are localized and hormone-dependent, and grow slowly. Patients with localized PCas have a nearly 100% 5-year survival rate; however, the 5-year survival rate of metastatic or progressive PCa is still dismal. N6-methyladenosine (m6A) is the most common post-transcriptional mRNA modification and is dynamically regulated by m6A regulators. A few studies have shown that the abnormal expression of m6A regulators is significantly associated with cancer progression and immune cell infiltration, but the roles of these regulators in PCa remain unclear. Here, we examined the expression profiles and methylation levels of 21 m6A regulators across the Cancer Genome Atlas (TCGA), 495 PCas by consensus clustering, and correlated the expression of m6A regulators with PCa progression and immune cell infiltration. Consensus clustering was applied for subtyping Pca samples into clusters based on the expression profiles of m6A regulators. Each subtype’s signature genes were obtained by a pairwise differential expression analysis. Featured pathways of m6A subtypes were predicted by Gene Ontology. The m6A score was developed to predict m6A activation. The association of the m6A score with patients’ survival, metastasis and immune cell infiltration was also investigated. We identified three distinct clusters in PCa based on the expression profiles of 21 m6A regulators by consensus clustering. The differential expression and pathway analyses on the three clusters uncovered the m6A regulators involved in metabolic processes and immune responses in PCa. Moreover, we developed an m6A score to evaluate the m6A regulator activation for PCa. The m6A score is significantly associated with Gleason scores and metastasis in PCa. The predictive capacity of the m6A score on PCa metastasis was also validated in another independent cohort with an area under the curve of 89.5%. Hence, our study revealed the critical role of m6A regulators in PCa progression and the m6A score is a promising predictive biomarker for PCa metastasis.

RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations

“…Many previous studies investigated the changes at the transcriptomic level, and limited focus was given to the proteomic expression of the m6A regulators, which closely correlates with their cellular function [30][31][32][33]. The current study unveils complex relationships between the transcriptional activity and protein expression of m6A methylation regulators, revealing little concordance between the transcriptomics and proteomics data.…”

Predicting prostate cancer recurrence: Introducing PCRPS, an advanced online web server

“…Predictive indicators for prostate cancer have been developed in the past few years, however, nearly all of them depend on a particular pathway, such as immunity, metabolism [ 52 ], and m6A methylation [ 53 ]. These indicators neglected information on other biological mechanisms that were critical to the development of prostate cancer.…”

Crafting a Personalized Prognostic Model for Malignant Prostate Cancer Patients Using Risk Gene Signatures Discovered through TCGA-PRAD Mining, Machine Learning, and Single-Cell RNA-Sequencing

“…The hallmarks of this tumor were characterized by uncontrolled cell proliferation [ 24 , 25 ], making the establishment of prognostic models based on molecular markers of programmed cell death and physiological process a hot topic in current risk model explorations. For example, predicting models based on crucial regulatory molecules of cuproptosis [ 26 ], steroid hormone biosynthesis [ 27 ], and m6A methylation [ 28 ] are well established, and their correlation with immune cell infiltration can also be analyzed. Disulfidptosis is a newly discovered form of programmed cell death, which is characterized by the inhibition of intracellular disulfide reductants and the significant enhancement of cell death caused by SLC7A11 under glucose starvation conditions, in contrast to the significant increase in cell death induced by thiol oxidation reagents such as diamide [ 29 ].…”