Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

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.