双氧化酶 1 和 NADPH 氧化酶 2 通过激活免疫反应对宫颈癌患者发挥有利作用。
Dual oxidase 1 and NADPH oxidase 2 exert favorable effects in cervical cancer patients by activating immune response.
机构信息
School of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, Republic of Korea.
Department of Clinical Medicine, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, Republic of Korea.
出版信息
BMC Cancer. 2019 Nov 9;19(1):1078. doi: 10.1186/s12885-019-6202-3.
BACKGROUND
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) not only can promote cancer progression, but also they have recently emerged as mediators of the mucosal immune system. However, the roles and clinical relevance of the collective or individual NADPH oxidase (NOX) family genes in cervical cancer have not been studied.
METHODS
We investigated the clinical significance of the NOX family genes using data from 307 patients with cervical cancer obtained from The Cancer Genome Atlas. Bioinformatics and experimental analyses were performed to examine NOX family genes in cervical cancer patients.
RESULTS
Dual Oxidase1 (DUOX1) and Dual Oxidase 2 (DUOX2) mRNA levels were upregulated 57.9- and 67.5-fold, respectively, in cervical cancer patients. The protein expression of DUOX1, DUOX2, and NOX2 also identified in cervical squamous cell carcinoma tissues. Especially, DUOX1 and DUOX2 mRNA levels were significantly increased in patients infected with human papillomavirus (HPV) 16. Moreover, high DUOX1 mRNA levels were significantly associated with both favorable overall survival and disease-free survival in cervical cancer patients. High NOX2 mRNA levels was significantly associated with favorable overall survival. Gene set enrichment analyses revealed that high DUOX1 and NOX2 expression was significantly correlated with the enrichment of immune pathways related to interferon (IFN)-alpha, IFN-gamma, and natural killer (NK) cell signaling. Cell-type identification by estimating relative subsets of known RNA transcript analyses indicated that the fraction of innate immune cells, including NK cells, monocytes, dendritic cells, and mast cells, was elevated in patients with high DUOX1 expression.
CONCLUSIONS
DUOX1 and NOX2 expression are associated with mucosal immunity activated in cervical squamous cell carcinoma and predicts a favorable prognosis in cervical cancer patients.
背景
烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶衍生的活性氧（ROS）不仅可以促进癌症的进展，而且最近还被认为是黏膜免疫系统的介质。然而，NADPH 氧化酶（NOX）家族基因的集体或个体在宫颈癌中的作用及其临床相关性尚未得到研究。
方法
我们使用从癌症基因组图谱中获得的 307 名宫颈癌患者的数据来研究 NOX 家族基因的临床意义。进行了生物信息学和实验分析，以检查宫颈癌患者中的 NOX 家族基因。
结果
双氧化酶 1（DUOX1）和双氧化酶 2（DUOX2）mRNA 水平分别上调了 57.9 倍和 67.5 倍。在宫颈鳞状细胞癌组织中也鉴定出 DUOX1、DUOX2 和 NOX2 的蛋白表达。特别是，在感染人乳头瘤病毒（HPV）16 的患者中，DUOX1 和 DUOX2 mRNA 水平显着增加。此外，DUOX1 mRNA 水平高与宫颈癌患者的总生存和无病生存均显着相关。高 NOX2 mRNA 水平与总生存良好显着相关。基因集富集分析表明，DUOX1 和 NOX2 表达高与干扰素（IFN）-α、IFN-γ和自然杀伤（NK）细胞信号相关的免疫途径的富集显着相关。通过估计已知 RNA 转录物分析的相对亚群来进行细胞类型鉴定表明，高 DUOX1 表达患者中固有免疫细胞（包括 NK 细胞、单核细胞、树突状细胞和肥大细胞）的分数升高。
结论
DUOX1 和 NOX2 的表达与宫颈鳞状细胞癌中激活的黏膜免疫有关，并预测宫颈癌患者的预后良好。
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