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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
GNPNAT1 是乳腺癌中与免疫浸润和免疫治疗结局相关的潜在生物标志物
英文原题：GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer.
查看英文原题
GNPNAT1 is a potential biomarker correlated with immune infiltration and immunotherapy outcome in breast cancer.
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研究概要
GNPNAT1 是 BRCA 潜在的诊断、预后生物标志物和新的干预靶点。
研究思路结论见上方概要
背景
氨基葡萄糖6-磷酸N-乙酰转移酶（GNPNAT1）是己糖胺生物合成途径中的关键酶，在乳腺癌（BRCA）中表达上调。然而，其在BRCA患者中的生物学功能及机制尚未被研究。
方法
本研究利用癌症基因组图谱（TCGA）数据库和基因表达综合数据库（GEO）分析GNPNAT1在BRCA组织与正常乳腺组织中的差异表达，并通过实时荧光定量PCR、Western blot和免疫组织化学进行验证。随后，基于TCGA数据库探讨GNPNAT1在BRCA中的潜在临床价值。通过基因本体论（基因本体）、京都基因与基因组百科全书（京都基因与基因组百科全书）、基因集变异分析（Gene Set Variation Analysis）等功能富集分析，探索GNPNAT1在BRCA中涉及的潜在信号通路和生物学功能。利用ESTIMATE、CIBERSORT和TISIDB数据库分析肿瘤免疫浸润情况，并采用TIDE评估免疫治疗应答评分。最后，采用Western blot、CCK-8和Transwell实验检测敲低GNPNAT1后乳腺癌细胞的增殖和侵袭能力。
结果
与正常组织相比，GNPNAT1在BRCA组织中表达上调，随后在不同细胞系和临床组织样本中得到验证。基于TCGA和GEO，GNPNAT1在BRCA中的过表达导致总生存期和疾病特异性生存期显著下降。功能富集分析表明，GNPNAT1高表达组中富集的通路包括柠檬酸循环、N-聚糖生物合成、DNA修复和基础转录因子。此外，GNPNAT1的过表达与免疫治疗反应以及CD8+ T细胞、B细胞、NK 细胞、树突状细胞和巨噬细胞的免疫细胞浸润水平呈负相关。敲低GNPNAT1会损害乳腺癌细胞的增殖和侵袭能力。
展开英文摘要原文
BACKGROUND
Glucosamine 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.
METHODS
In 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.
RESULTS
GNPNAT1 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.
CONCLUSION
GNPNAT1 is a potential diagnostic, prognostic biomarker and novel target for intervention in BRCA.
论文信息
- 作者
- Yuan R、Zhang Y、Wang Y、Chen H、Zhang R、Hu Z、Chai C、Chen T
- 单位
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Frontiers in immunology2023
- 原文标识
- PubMed 37215111 · DOI 10.3389/fimmu.2023.1152678
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