Neuromedin U receptor 1 deletion leads to impaired immunotherapy response and high malignancy in colorectal cancer

神经调节素U受体1缺失会导致结直肠癌免疫治疗反应受损和恶性程度升高。

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Abstract

Colorectal cancer (CRC) exhibits significant heterogeneity, impacting immunotherapy efficacy, particularly in immune desert subtypes. Neuromedin U receptor 1 (NMUR1) has been reported to perform a vital function in immunity and inflammation. Through comprehensive multi-omics analyses, we have systematically characterized NMUR1 across various tumors, assessing expression patterns, genetic alterations, prognostic significance, immune infiltration, and pathway associations at both the bulk sequencing and single-cell scales. Our findings demonstrate a positive correlation between NMUR1 and CD8+ T cell infiltration, with elevated NMUR1 levels in CD8+ T cells linked to improved immunotherapy outcomes in patients with CRC. Further, we have validated the NMUR1 expression signature in CRC cell lines and patient-derived tissues, revealing its interaction with key immune checkpoints, including lymphocyte activation gene 3 and cytotoxic T-lymphocyte-associated protein 4. Additionally, NMUR1 suppression enhances CRC cell proliferation and invasiveness. Our integrated analyses and experiments open new avenues for personalized immunotherapy strategies in CRC treatment. Keywords: Bioinformatics; Cancer; Microenvironment; Molecular biology; Therapeutics.

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