Wierzbicki Piotr M, Czajkowski Mateusz, Kotulak-Chrząszcz Anna, Bukowicz Justyna, Dzieciuch Klaudia, Sokołowska-Wojdyło Małgorzata, Kmieć Zbigniew, Matuszewski Marcin
Department of Histology, Medical University of Gdańsk, 80-211 Gdańsk, Poland.
Department of Urology, Medical University of Gdańsk, Mariana Smoluchowskiego 17 Street, 80-214 Gdańsk, Poland.
J Clin Med. 2022 Dec 7;11(24):7254. doi: 10.3390/jcm11247254.
The nuclear factor-κB transcription factors 1 and 2 (NFKB1 and NFKB2) are key components of the NF-κB pathway, which responds to inflammatory signals. Since the NFKB1/2 factors are activated via different inflammatory molecules, we aimed to check their expression levels in penile cancer (PC), penile dermatoses: lichen sclerosus (PLS) and zoon balanitis (ZB).
Skin biopsies from altered and healthy looking foreskin were obtained from 59 (49 LS; early PLS: 13, moderate PLS: 32, severe PLS: 4; 6 PC; 4 ZB) and unchanged foreskin from 13 healthy control adult males undergoing circumcision. NFKB1/2 mRNA levels were quantified by qPCR.
The highest levels of NFKB1 and NFKB2 were observed in PC, ca. 22 and 3.5 times higher than in control, respectively. NFKB1 expression was correlated with PLS progression (rs = 0.667) and was ca. 20 times higher in advanced PLS than in controls and early PLS. Occurrence of micro-incontinence was associated with elevated NFKB1 levels in PLS.
This is the first study regarding gene profiles of NFKB1/2 in PC and penile dermatoses. New drugs targeting modulation of canonical-activated NF-κB pathway should be studied and introduced to the treatment of PLS and PC apart from other treatments.
核因子-κB转录因子1和2(NFKB1和NFKB2)是NF-κB信号通路的关键组成部分,该信号通路对炎症信号作出反应。由于NFKB1/2因子通过不同的炎症分子被激活,我们旨在检测它们在阴茎癌(PC)、阴茎皮肤病:硬化性苔藓(PLS)和浆细胞性龟头炎(ZB)中的表达水平。
从59例患者(49例LS;早期PLS:13例,中度PLS:32例,重度PLS:4例;6例PC;4例ZB)病变及外观正常的包皮以及13例接受包皮环切术的健康成年男性未改变的包皮获取皮肤活检样本。通过qPCR对NFKB1/2 mRNA水平进行定量。
在PC中观察到NFKB1和NFKB2的最高水平,分别约比对照组高22倍和3.5倍。NFKB1表达与PLS进展相关(rs = 0.667),在晚期PLS中比对照组和早期PLS高约20倍。微失禁的发生与PLS中NFKB1水平升高相关。
这是第一项关于PC和阴茎皮肤病中NFKB1/2基因谱的研究。除其他治疗方法外,应研究并引入靶向调节经典激活的NF-κB信号通路的新药用于治疗PLS和PC。