Objective: To comprehensively explore the impact of Mono-ADP-ribosyltransferases-1 expression on both prognosis and the intricate landscape of the tumor immune microenvironment across diverse cancer types, our study seeks to delve into the multifaceted interplay between Mono-ADP-ribosyltransferases-1 expression levels and their implications for clinical outcomes and the dynamic milieu of immune responses within tumors. Methods: Genomic, transcriptomic, and clinical datasets spanning diverse cancer types were meticulously curated from The Cancer Genome Atlas and Genotypic Tissue Expression repositories. Initially, our inquiry focused on discerning the prognostic significance and immunological implications of Mono-ADP-ribosyltransferases-1 expression across this heterogeneous spectrum of malignancies. Subsequently, we scrutinized the relationships between Mono-ADP-ribosyltransferases-1 expression levels and a spectrum of factors including RNA modification genes, genetic mutations, and the emergent concept of tumor stemness. Employing functional enrichment analyses, we endeavored to unravel the underlying mechanistic pathways modulated by Mono-ADP-ribosyltransferases-1. Leveraging Bayesian co-localization analysis, we sought to discern the spatial convergence of Mono-ADP-ribosyltransferases-1 expression particularly within the context of digestive tract tumors. Lastly, to corroborate our findings, we conducted in vitro experiments, specifically focusing on Gastric Cancer, thus corroborating the putative oncogenic role attributed to Mono-ADP-ribosyltransferases-1 in this malignancy. Results: Across diverse tumor types, Mono-ADP-ribosyltransferases-1 expression exhibits distinctive patterns compared to normal and adjacent tissues, thereby intertwining with the prognostic outcomes of numerous cancer patients. Noteworthy findings from our immune role identification underscore the pivotal involvement of Mono-ADP-ribosyltransferases-1 in the landscape of tumor immunotherapy. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis elucidates the enrichment of Mono-ADP-ribosyltransferases-1-associated genes predominantly within the NF-kB, Foxo, and PI3K-Akt signaling cascades, shedding light on potential mechanistic pathways underlying its influence. Bayesian co-localization analysis unveils a compelling genetic correlation between Mono-ADP-ribosyltransferases-1 and digestive tract tumors, accentuating its relevance within this specific oncological domain. Importantly, experimental validation attests to the therapeutic promise of targeting Mono-ADP-ribosyltransferases-1 in the treatment paradigm of gastric cancer, thereby underscoring its potential as a viable therapeutic target deserving of further exploration and clinical translation. Conclusion: This comprehensive pan-cancer analysis unveils crucial insights into the intricate role played by Mono-ADP-ribosyltransferases-1 in the tumorigenesis of diverse malignancies, thereby establishing a robust theoretical framework for subsequent in-depth investigations. Leveraging these insights, targeting Mono-ADP-ribosyltransferases-1-related signaling pathways within the dynamic tumor microenvironment emerges as a promising avenue for novel therapeutic interventions in the realm of tumor immunotherapy. By delineating the interplay between Mono-ADP-ribosyltransferases-1 expression and tumorigenic processes across various cancer types, this study paves the way for innovative therapeutic strategies aimed at disrupting oncogenic signaling cascades and bolstering immune-mediated antitumor responses.
