Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London, W12 0NN, UK.
Department of Pathology, Alexandria Faculty of Medicine, Alexandria, Egypt.
J Egypt Natl Canc Inst. 2022 Jun 6;34(1):24. doi: 10.1186/s43046-022-00125-4.
Ovarian cancer has the highest mortality amongst all gynaecological malignancies, with around two-thirds of patients diagnosed with advanced disease due to late presentation. Furthermore, around 90% of patients develop recurrence and eventually become chemoresistant. Therefore, there is a high demand to identify biomarkers specific to this disease for screening for early detection, as well as new therapeutic targets. Tight junctions (TJs) regulate paracellular permeability and are vital in establishing epithelial cell polarity. One hallmark of tumorigenesis is the loss of TJs, with loss of cell-to-cell adhesion. Claudins are integral TJ membrane proteins, which have been found to play a critical role in maintaining the TJ's barrier function. Furthermore, claudin-3 (CLDN3) and claudin-4 (CLDN4) are overexpressed in ovarian cancer. This article aims to explore the biological role of CLDN3 and CLDN4 and their potential in different aspects of the management of ovarian cancer.
CLDN3 and CLDN4 have been shown to be effective markers for the early detection of ovarian cancer. Whilst there is difficulty in screening for both claudins in serum, their assessment by gene expression analysis and immunohistochemical methods shows promising potential as diagnostic and prognostic biomarkers for ovarian cancer. The localisation and overexpression of claudins, such as CLDN3, have been shown to correlate with poorer survival outcomes. The added value of combining claudins with other markers such as CA125 for diagnosis has also been highlighted. Therapeutically, CLDN3 and more so CLDN4 have been shown to be effective targets of Clostridium perfringens enterotoxin (CPE). Interestingly, CPE has also been shown to resensitise chemoresistant tumours to therapy.
This review presents the diagnostic and prognostic potential of CLDN3 and CLDN4 and their emerging role as therapeutic targets in ovarian cancer. Clinical trials are required to validate the promising results of the in vitro and in vivo studies for CLDN3 and CLDN4, possibly adding onto current ovarian cancer management.
卵巢癌是妇科恶性肿瘤中死亡率最高的，约三分之二的患者因晚期出现症状而被诊断为晚期疾病。此外，约 90%的患者会复发并最终产生化疗耐药性。因此，人们强烈需要确定针对这种疾病的生物标志物，用于早期发现的筛查，以及新的治疗靶点。紧密连接（TJs）调节细胞旁通透性，对于建立上皮细胞极性至关重要。肿瘤发生的一个标志是 TJ 的丧失，即细胞间黏附的丧失。 Claudin 是 TJ 膜的重要组成部分，已发现其在维持 TJ 的屏障功能方面发挥着关键作用。此外，Claudin-3 (CLDN3) 和 Claudin-4 (CLDN4) 在卵巢癌中过度表达。本文旨在探讨 CLDN3 和 CLDN4 的生物学作用及其在卵巢癌管理不同方面的潜在应用。
CLDN3 和 CLDN4 已被证明是卵巢癌早期检测的有效标志物。虽然在血清中同时检测这两种 Claudin 具有一定难度，但通过基因表达分析和免疫组织化学方法评估它们，作为卵巢癌的诊断和预后生物标志物具有很大的潜力。Claudin，如 CLDN3 的定位和过表达与较差的生存结果相关。将 Claudin 与 CA125 等其他标志物结合用于诊断的附加价值也得到了强调。在治疗方面，CLDN3 更确切地说是 CLDN4 已被证明是梭状芽胞杆菌肠毒素（CPE）的有效靶点。有趣的是，CPE 还被证明能使化疗耐药肿瘤重新对治疗敏感。
本综述介绍了 CLDN3 和 CLDN4 的诊断和预后潜力及其作为卵巢癌治疗靶点的新作用。需要进行临床试验来验证 CLDN3 和 CLDN4 的体外和体内研究的有前途的结果，这可能会对当前的卵巢癌管理有所补充。
