Correlation of NQO1 and Nrf2 in Female Genital Tract Cancer and Their Precancerous Lesions (Cervix, Endometrium and Ovary)

Abstract

BackgroundNAD (P) H/quinone oxidoreductase 1 (NQO1) is a metabolizing enzyme that detoxifies chemical stressors and antioxidants. Nuclear factor erythroid 2-related factor 2 (NrF2) is an important transcriptional activator involved in the cellular defense mechanisms against oxidative stress.MethodsThe immunohistochemical expression of NQO1 and Nrf2 in 80 cervical, 80 endometrial and 100 ovarian specimens with different lesions was studied. Then we study the relation of both NQO1 and Nrf2 expression and clinicopathological features of carcinoma cases.ResultsImmunohistochemical stain showed that NQO1 and Nrf2 were highly expressed in carcinoma compared with normal and precancerous lesions. Significant positive correlations were found between the mean expression of NQO1 and Nrf2 in different lesions. Moreover, there was significant correlation between the high level of NQO1 and Nrf2 expression and high tumor grade in cervical and endometrial carcinoma cases. Nrf2 expression was significant with advanced stage in endometrial and ovarian carcinomas.ConclusionsNQO1 and Nrf2 might be new biomarkers for early diagnosis and prognostic evaluation as well as being targets for therapy in patients with tumors in female genital tract.

Nuclear factor erythroid 2‐related factor 2 in human papillomavirus‐related cancers

“…74 Thus, Nrf2 expression is associated with its activation in the late stages of cervical cancer and cervical cell lines. Osman et al 75 also found that Nrf2 is overexpressed in high tumour grade of cervical carcinoma cases, which correlates with high levels of its target NQO1. Kontostathi et al 76 demostrated that Nrf2 is activated in SiHa cells and cervical cancer samples.…”

The Dual Role of NRF2 Transcription Factor in Female Cancer

“…Nrf2 was also related to ovarian cancer once NQO1 and NRF2 were highly expressed compared to normal and precancerous lesions, showing a positive correlation across different types of lesions. NRF2 expression was observed in both the nucleus and cytoplasm of ovarian cells, with a significant increase observed as the ovarian carcinoma stage advances [50]. NRF2 is correlated to…”

From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration

“…As a result, several cancer types have the NRF2/KEAP1 pathway as a primary target for chemotherapy (Zimta et al, 2019;Tossetta et al, 2022). In fact, studies have shown that higher levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and NRF2 expression are associated with higher-grade cancers such as endometrial and cervical carcinomas as opposed to healthy tissue and precancerous lesions (Osman et al, 2015). NQO1 and NRF2 may be valuable biomarkers for early diagnosis, prognostic, and Frontiers in Pharmacology frontiersin.org therapeutic strategies in patients with cervical and endometrial carcinomas, in line with additional research showing that NRF2 overexpression was significantly associated with high-grade and advanced-stage endometrial and ovarian carcinomas (Cho et al, 2017;Tossetta et al, 2022;Tossetta and Marzioni, 2023).…”