Identification of m6A suppressor EIF4A3 as a novel cancer prognostic and immunotherapy biomarker through bladder cancer clinical data validation and pan-cancer analysis

Abstract

AbstractEIF4A3 represents a novel m6A suppressor that exerts control over the global m6A mRNA modification level, therefore influencing gene destiny. Despite increasing evidence that highlights a pivotal role of EIF4A3 in tumor progression and immunity, a comprehensive pan-cancer analysis of EIF4A3 has yet to be conducted, in order to ascertain whether EIF4A3 could be a viable biomarker for cancer screening, prediction of prognosis, and to facilitate accurate therapy design in various human malignancies. We analyzed the expression levels of EIF4A3 in bladder cancer compared to para-cancer tissue. Subsequently survival analysis was conducted to ascertain the potential association between EIF4A3 expression and patient prognosis. To further corroborate this evidence, we conducted an extensive data mining process of several publicly available databases, including UCSC Xena database, TCGA, and GTEx. Raw data from the UCSC Xena database was processed using online tools to obtain results that could be subjected to further analysis. Our study unveiled a considerable increase in the expression levels of EIF4A3 in bladder cancer compared to para-cancer tissue. Subsequent validation experiments confirmed that bladder cancer patients exhibiting higher levels of EIF4A3 expression have significantly worse prognostic outcomes. Next, our pan-cancer analysis found that the expression level of EIF4A3 is significantly higher in most cancers. Notably, high expression levels of EIF4A3 were negatively associated with patient prognosis across various cancer types. Furthermore, as a novel m6A suppressor, EIF4A3 was found to be correlated with numerous RNA modification genes in multiple cancer types. Meanwhile, analysis of publicly available databases revealed that EIF4A3 expression was significantly related to immune score and immune cell levels in most cancer types. Interestingly, EIF4A3 was also identified as a superior immunotherapy biomarker when compared to several traditional immunotherapy biomarkers. Lastly, genetic alterations analysis revealed that amplification was the most frequently occurring abnormality in the EIF4A3 gene. EIF4A3 emerges as a promising biomarker with the potential to significantly enhance tumor screening, prognostic evaluation, and the design of individualized treatment strategies across a diverse array of malignancies.