Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan.
Hubei Cancer Clinical Study Centre and Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan.
Eur J Histochem. 2021 Apr 28;65(2):3228. doi: 10.4081/ejh.2021.3228.
Condyloma acuminata (CA) are benign anogenital warts caused by human papillomavirus (HPV) infection with a high recurrence rate. Despite its high contagiousness, high recurrence rate and potential for malignant transformation, effective treatments for CA have not yet been developed. Accordingly, it is necessary to clarify the mechanisms underlying CA development. Zinc (Zn) is stably maintained in the weight of human body. Skin is the third most Zn-abundant tissue in the body. Zn is present as a divalent ion (Zn2+) in cells and does not need a redox reaction upon crossing the cellular membrane. Zn transporters (ZnTs; SLC30A) and Irt-like proteins (ZIPs; SLC39A) are involved in Zn2+ efflux and uptake, respectively. ZnT1 is one of the ZnTs, which associates with the development of HPV. However, the role of ZnT1 regulation in the CA caused by HPV infection remains unknown. A multigroup case-control study was designed to investigate the expression and significance of the ZnT1 in patients with CA infected with HPV and in normal vulva controls. ZnT1 was assessed by immunohistochemistry in 44 patients with CA at Zhongnan Hospital of Wuhan University 2019-2020. Samples were analyzed by paraffin embedding and sectioning and hematoxylin-eosin and immunohistochemical staining. Immunohistochemical methods detected specific, dark brown, positive staining of ZnT1 in the keratinocytes of epidermis. We verified that the expression levels of ZnT1 that interact with HPV were upregulated in the CA groups independently of genotype compared with the control group. And then we found that the HPV risk grade in CA patients has a certain correlation with ZnT1 expression. These findings showed that HPV infection upregulated the expression of ZnT1 in CA. Additionally, there were obvious differences in the expression of ZnT1 between the different HPV risk grade infection groups. The higher the HPV risk grade, the stronger the ZNT1 protein expression. This study provided new insights into the sign pathway to HPV infection.
尖锐湿疣（CA）是由人乳头瘤病毒（HPV）感染引起的良性肛门生殖器疣，具有较高的复发率。尽管 CA 具有高度传染性、高复发率和潜在的恶性转化风险，但尚未开发出有效的 CA 治疗方法。因此，有必要阐明 CA 发病机制。锌（Zn）在人体体重中稳定维持。皮肤是人体中第三大富含 Zn 的组织。Zn 以二价离子（Zn2+）的形式存在于细胞中，穿过细胞膜时不需要氧化还原反应。Zn 转运蛋白（ZnTs；SLC30A）和 Irt 样蛋白（ZIPs；SLC39A）分别参与 Zn2+的外排和摄取。ZnT1 是 ZnTs 之一，与 HPV 的发育有关。然而，ZnT1 调节在 HPV 感染引起的 CA 中的作用尚不清楚。设计了一项多组病例对照研究，以调查 HPV 感染患者和正常外阴对照中 ZnT1 的表达和意义。2019-2020 年，武汉大学中南医院对 44 例 CA 患者进行了 ZnT1 免疫组化评估。通过石蜡包埋和切片、苏木精-伊红和免疫组织化学染色对样本进行分析。免疫组织化学方法检测到表皮角蛋白细胞中 ZnT1 的特异性、深棕色、阳性染色。我们验证了与 HPV 相互作用的 ZnT1 表达水平在 CA 组中独立于基因型而上调，与对照组相比。然后我们发现 CA 患者的 HPV 风险等级与 ZnT1 表达有一定的相关性。这些发现表明 HPV 感染上调了 CA 中 ZnT1 的表达。此外，不同 HPV 风险等级感染组之间 ZnT1 的表达存在明显差异。HPV 风险等级越高，ZNT1 蛋白表达越强。本研究为 HPV 感染的信号通路提供了新的见解。
