Borowczak Jędrzej, Łaszczych Dariusz, Olejnik Katarzyna, Michalski Jakub, Gutowska Anna, Kula Monika, Bator Anita, Sekielska-Domanowska Marta, Makarewicz Roman, Marszałek Andrzej, Szylberg Łukasz, Bodnar Magdalena
Department of Clinical Oncology, Oncology Centre Prof. Franciszek Łukaszczyk Memorial Hospital, 85-796 Bydgoszcz, Poland.
Department of Tumor Pathology and Pathomorphology, Oncology Centre Prof. Franciszek Łukaszczyk Memorial Hospital, 85-796 Bydgoszcz, Poland.
Pharmaceuticals (Basel). 2024 Sep 30;17(10):1304. doi: 10.3390/ph17101304.
Claudins are tight junction proteins partaking in epithelial-mesenchymal transition and cancer progression. In this study, we investigated the expression patterns of claudin-1 and claudin-4 in thyroid pathologies, discussed their links with the pathogenesis of thyroid cancers, and reviewed the therapeutic potential of targeting claudins in cancers. The research group 162 cores of thyroid samples from patients (70 female and 11 male) diagnosed with thyroid adenoma, goiter, papillary, medullary, and anaplastic thyroid cancers. All samples were stained for the expression of claudin-1 and claudin-4, and the analysis of IHC was performed. Goiter samples showed negative claudin-1 and mostly positive expression of claudin-4. Papillary thyroid cancer and thyroid adenoma showed positive expression of claudin-1, while claudin-4 was positive in papillary thyroid cancers, goiters, and adenomas. In The Cancer Genome Atlas cohort, claudin-1 and claudin-4 were overexpressed in papillary thyroid cancer compared to normal thyroid tissues. Patients with high claudin-1 expression had significantly lower 5-year overall survival than patients with low claudin-1 levels (86.75% vs. 98.65, respectively). In multivariate analysis, high claudin-1 expression (HR 7.91, CI 95% 1.79-35, = 0.006) and advanced clinical stage remained statistically significant prognostic factors of poor prognosis in papillary thyroid cancer. The pattern of claudin-1 staining was pathology-specific and changed between cancers of different histology. This phenomenon may be associated with the different pathogenesis of thyroid cancers and early metastasis. The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.
紧密连接蛋白参与上皮-间质转化和癌症进展。在本研究中，我们调查了紧密连接蛋白-1和紧密连接蛋白-4在甲状腺病变中的表达模式，讨论了它们与甲状腺癌发病机制的联系，并综述了靶向紧密连接蛋白在癌症治疗中的潜力。研究小组对162例来自被诊断患有甲状腺腺瘤、甲状腺肿、乳头状癌、髓样癌和未分化甲状腺癌患者（70名女性和11名男性）的甲状腺样本芯块进行了研究。所有样本均进行紧密连接蛋白-1和紧密连接蛋白-4表达的染色，并进行免疫组化分析。甲状腺肿样本紧密连接蛋白-1呈阴性，紧密连接蛋白-4大多呈阳性表达。甲状腺乳头状癌和甲状腺腺瘤紧密连接蛋白-1呈阳性表达，而紧密连接蛋白-4在甲状腺乳头状癌、甲状腺肿和腺瘤中呈阳性。在癌症基因组图谱队列中，与正常甲状腺组织相比，紧密连接蛋白-1和紧密连接蛋白-4在甲状腺乳头状癌中过表达。紧密连接蛋白-1高表达的患者5年总生存率显著低于紧密连接蛋白-1低水平的患者（分别为86.75%和98.65%）。在多变量分析中，紧密连接蛋白-1高表达（风险比7.91，95%置信区间1.79 - 35，P = 0.006）和临床晚期仍然是甲状腺乳头状癌预后不良的统计学显著预后因素。紧密连接蛋白-1染色模式具有病理特异性，在不同组织学类型的癌症之间有所变化。这种现象可能与甲状腺癌不同的发病机制和早期转移有关。紧密连接蛋白-1和紧密连接蛋白-4的缺失是更具侵袭性癌症的特征。几项研究显示了靶向紧密连接蛋白在癌症治疗中的益处，但将其应用于临床实践还需要进一步试验。
