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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作者:Yulai Zhou ,Xiangyang Zhang ,Yan Gao ,Yinghui Peng ,Ping Liu ,Yihong Chen ,Cao Guo ,Gongping Deng ,Yanhong Ouyang ,Yan Zhang ,Ying Han ,Changjing Cai ,Hong Shen ,Le Gao ,Shan Zeng

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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