GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer

作者全名："Yuan, Renjie; Zhang, Yulu; Wang, Yange; Chen, Hongling; Zhang, Ruiming; Hu, Zhiyuan; Chai, Chengsen; Chen, Tingmei"

作者地址："[Yuan, Renjie; Zhang, Yulu; Wang, Yange; Chen, Hongling; Zhang, Ruiming; Chai, Chengsen; Chen, Tingmei] Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Minist Educ, Chongqing, Peoples R China; [Hu, Zhiyuan] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Key Lab Standardizat & Measurement Nanotechnol, Natl Ctr Nanosci & Technol,Ctr Excellence Nanosci, Beijing, Peoples R China"

通信作者："Chai, CS; Chen, TM (通讯作者)，Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Minist Educ, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000989274400001

JCR分区：Q1

影响因子：7.3

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：GNPNAT1; breast cancer; biomarker; tumor-infiltration immune cells; immune checkpoints inhibitors; immunotherapy response

摘要："BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a crucial enzyme involving hexosamine biosynthesis pathway and is upregulated in breast cancer (BRCA). However, its biological function and mechanism on patients in BRCA have not been investigated. MethodsIn this study, the differential expression of GNPNAT1 was analyzed between BRCA tissues and normal breast tissues using the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, which was validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. Then, the potential clinical value of GNPNAT1 in BRCA was investigated based on TCGA database. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis, were performed to explore the potential signaling pathways and biological functions involved in GNPNAT1 in BRCA. Tumor immune infiltration was analyzed using ESTIMATE, CIBERSORT and TISIDB database; and immune therapy response scores were assessed using TIDE. Finally, Western blot, Cell counting kit-8 and Transwell assay were used to determine the proliferation and invasion abilities of breast cancer cells with GNPNAT1 knockdown. ResultsGNPNAT1 was up-regulated in BRCA tissues compared with normal tissues which was subsequently verified in different cell lines and clinical tissue samples. Based on TCGA and GEO, the overexpression of GNPNAT1 in BRCA contributed to a significant decline in overall survive and disease specific survive. Functional enrichment analyses indicated that the enriched pathways in high GNPNAT1 expression group included citrate cycle, N-glycan biosynthesis, DNA repair, and basal transcription factors. Moreover, the overexpression of GNPNAT1 was negatively correlated with immunotherapy response and the levels of immune cell infiltration of CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. Knockdown of GNPNAT1 impairs the proliferation and invasion abilities of breast cancer cells. ConclusionGNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA."

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