Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

SIMPLE SUMMARY: RRM2 is a crucial subunit of ribonucleotide reductase. In this article, we provided a comprehensive analysis of RRM2 with immune infiltration in pan-cancer. We focused on the hotspots of ferroptosis-related gene RRM2 and immunotherapy. Via bioinformatics analysis, multiple indicators suggested that RRM2 high expression may enhance immunotherapy sensitivity. For the first time, we systematically analyzed the role of RRM2 in pan-cancer. We provided the prospect of RRM2 and immunotherapy for pan-cancer. Additionally, we proved the expression pattern, clinical value, prognostic value and potential pathways of RRM2 with different platforms. In particular, we confirmed RRM2 expression and function in bladder cancer in our clinical samples and cell lines. Collectively, we found that RRM2 is a novel prognostic biomarker, and these findings may aid in an improved understanding of the role of RRM2 and its clinical application in human cancers. ABSTRACT: As a crucial subunit of ribonucleotide reductase, RRM2 plays a significant part in DNA synthesis. This study aimed to elucidate the comprehensive landscape of RRM2 in human cancers. With different bioinformatics platforms, we investigated the expression pattern, prognostic significance, mutational landscapes, gene interaction network, signaling pathways and immune infiltration of RRM2 in tumors. We found that RRM2 expression was predominantly up-expressed in tumor tissues in most tumors. Concurrently, RRM2 expression was significantly associated with worse prognosis and tumor stage across TCGA cancers. Moreover, RRM2 high levels were critically associated with the infiltration of natural killer T cells and immune scores. RRM2 was positively related to immune checkpoints, tumor mutation burden, microsatellite instability, neoantigen, and cytotoxic T lymphocyte in several cancers, predicting effective response to immunotherapy. Meanwhile, a strong co-expression of RRM2 with immune-related genes was observed. Additionally, multiple Cox regression analysis showed that RRM2 was an independent prognostic factor in bladder cancer (BLCA). Eventually, we verified that RRM2 was overexpressed in BLCA clinical samples and cell lines. Blocking RRM2 could suppress BLCA cells’ growth and proliferation while enhancing sensitivity to cisplatin. This study provided a new perspective for understanding RRM2 in cancers and new strategies for tumor immunotherapy.