Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Ribonucleotide reductase M2 (RRM2) is essential for DNA synthesis.
• Understanding RRM2's role in human cancers is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To comprehensively analyze the expression, prognostic value, and immune-related functions of RRM2 across various human cancers.
• To investigate RRM2's potential as a therapeutic target, particularly in bladder cancer (BLCA).

Main Methods:

• Utilized multiple bioinformatics platforms to analyze RRM2 expression, mutations, and gene interactions.
• Assessed the correlation between RRM2 levels and tumor-infiltrating immune cells, immune scores, and immunotherapy response markers.
• Performed survival analysis and Cox regression for prognostic significance.
• Validated RRM2 expression and therapeutic potential in BLCA cell lines and clinical samples.

Main Results:

• RRM2 was predominantly upregulated in tumor tissues across most cancers.
• Higher RRM2 expression correlated with worse prognosis, advanced tumor stage, and increased infiltration of natural killer T cells.
• RRM2 levels were associated with immune checkpoints, tumor mutation burden, microsatellite instability, neoantigen load, and cytotoxic T lymphocytes, suggesting immunotherapy potential.
• RRM2 was identified as an independent prognostic factor in BLCA.
• RRM2 overexpression was confirmed in BLCA samples, and its inhibition suppressed tumor growth and enhanced cisplatin sensitivity.

Conclusions:

• RRM2 is a significant pan-cancer oncoprotein with prognostic and immunotherapeutic implications.
• Targeting RRM2 represents a promising strategy for enhancing cancer treatment, especially in bladder cancer.
• This study provides a foundation for RRM2-targeted cancer therapies and immunotherapies.