Dual oxidase 1 and NADPH oxidase 2 exert favorable effects in cervical cancer patients by activating immune response

Abstract

BackgroundNicotinamide 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.MethodsWe 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.ResultsDual 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.ConclusionsDUOX1 and NOX2 expression are associated with mucosal immunity activated in cervical squamous cell carcinoma and predicts a favorable prognosis in cervical cancer patients.

Extracellular Vesicles Derived from Induced Pluripotent Stem Cells Promote Renoprotection in Acute Kidney Injury Model

“…Interestingly, it has been previously reported that post-AKI rats had an increased expression of other pro-oxidant genes such as LPO, myeloperoxidase, and DUOX1 [51]. Moreover, gene set enrichment analyses in IRI condition revealed that high DUOX1 expression is significantly correlated with the enrichment of immune pathways related to interferon (IFN)-alpha, IFN-gamma, and natural killer (NK) cell signalling [52].…”

29 immune-related genes pairs signature predict the prognosis of cervical cancer patients

“…7D, 9C, 10I). Sang Yeon Cho et al Found that duox1 is highly expressed in cervical squamous cell carcinoma and can play a good prognostic role by increasing the amount of innate immune cells 54 . The analysis also showed that DUOX1 is highly expressed in tumor tissues and related to age and grade (Figs.…”

Identification of Core Genes Involved in the Progression of Cervical Cancer Using an Integrative mRNA Analysis

“…Although TOM1L1 regulates the oncoprotein ERBB2-driven cell invasion with metastatic phenotypes in breast cancer [ 33 ], there is no available information on the role of this gene in CC. Another gene predicting overall survival is DOXO1 (Dual oxidase 1), whose overexpression has been reported to promote favorable effects in CC patients via immune response activation [ 34 ]. In this study, we have observed that increased expression levels for this dual gene are related to a better prognostic.…”

“…Another gene detected in this study to be involved in CC pathogenesis is DUOX1. This gene plays a significant role in host mucosal immunity by producing hydrogen peroxide, thus serving as the first line of defense to HPV invasion, particularly in cervical cancer [ 34 ]. Yet another critical gene identified in this study is VEGF.…”