全癌症和单细胞分析揭示出NQO1的预后价值和免疫反应。
Pan-cancer and single-cell analysis reveal the prognostic value and immune response of NQO1.
发表日期:2023
作者:
Liping Shen, Shan Jiang, Yu Yang, Hongli Yang, Yanchun Fang, Meng Tang, Rangteng Zhu, Jiaqin Xu, Hantao Jiang
来源:
Frontiers in Cell and Developmental Biology
摘要:
背景:高表达的NAD(P)H:喹啉喹挪氧化酶1(NQOI)基因与肿瘤进展、侵袭性、药物抗性和患者预后不良相关联。多数研究描述了NQO1在某些类型和有限样本中的生物学功能,但对NQO1在全癌层面的功能和临床重要性的全面理解较为缺乏。需要更多的研究来了解NQO1在肿瘤浸润和各种癌症中的免疫检查点抑制剂的作用。方法:从公共数据库下载了33种全癌NQO1表达数据,并与预后、病理分期、性别、免疫细胞浸润、肿瘤突变负荷、微卫星不稳定性、免疫检查点、富集途径和半最大抑制浓度(IC50)进行关联分析。结果:研究结果表明,NQO1基因在大多数癌症类型中明显上调。Cox回归分析显示,NQO1基因的过表达与胶质瘤、葡萄膜黑色素瘤、头颈部鳞状细胞癌、肾脏乳头状细胞癌和肾上腺皮质癌的不良生存相关。NQO1 mRNA表达与浸润免疫细胞和检查点分子水平呈正相关。单细胞分析揭示了膀胱尿道上皮癌、浸润性乳腺癌和结直肠癌中NQO1 mRNA表达水平与免疫细胞和基质细胞浸润之间的潜在关系。与此相反,各种药物(17-AAG、Lapatinib、Trametinib、PD-0325901)与NQO1 mRNA表达水平呈负相关。结论:NQO1表达与多种癌症类型的预后、免疫浸润和药物抗性密切相关。抑制NQO1相关信号通路可能为新的癌症靶向治疗策略提供有希望的方向。版权所有 © 2023 Shen, Jiang, Yang, Yang, Fang, Tang, Zhu, Xu and Jiang.
Background: Overexpression of the NAD(P)H: Quinone Oxidoreductase 1 (NQOI) gene has been linked with tumor progression, aggressiveness, drug resistance, and poor patient prognosis. Most research has described the biological function of the NQO1 in certain types and limited samples, but a comprehensive understanding of the NQO1's function and clinical importance at the pan-cancer level is scarce. More research is needed to understand the role of NQO1 in tumor infiltration, and immune checkpoint inhibitors in various cancers are needed. Methods: The NQO1 expression data for 33 types of pan-cancer and their association with the prognosis, pathologic stage, gender, immune cell infiltration, the tumor mutation burden, microsatellite instability, immune checkpoints, enrichment pathways, and the half-maximal inhibitory concentration (IC50) were downloaded from public databases. Results: Our findings indicate that the NQO1 gene was significantly upregulated in most cancer types. The Cox regression analysis showed that overexpression of the NQO1 gene was related to poor OS in Glioma, uveal melanoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, and adrenocortical carcinoma. NQO1 mRNA expression positively correlated with infiltrating immune cells and checkpoint molecule levels. The single-cell analysis revealed a potential relationship between the NQO1 mRNA expression levels and the infiltration of immune cells and stromal cells in bladder urothelial carcinoma, invasive breast carcinoma, and colorectal cancer. Conversely, a negative association was noted between various drugs (17-AAG, Lapatinib, Trametinib, PD-0325901) and the NQO1 mRNA expression levels. Conclusion: NQO1 expression was significantly associated with prognosis, immune infiltrates, and drug resistance in multiple cancer types. The inhibition of the NQO1-dependent signaling pathways may provide a promising strategy for developing new cancer-targeted therapies.Copyright © 2023 Shen, Jiang, Yang, Yang, Fang, Tang, Zhu, Xu and Jiang.