Ouban Abderrahman, Ameer Omar Z, Quek Ko Jin, Arafah Maria A, Raddaoui Layla
Pathology and Molecular Medicine, Alfaisal University College of Medicine, Riyadh, SAU.
Pharmaceutical Sciences, Alfaisal University College of Pharmacy, Riyadh, SAU.
Cureus. 2023 Mar 24;15(3):e36648. doi: 10.7759/cureus.36648. eCollection 2023 Mar.
Background Triple-negative breast cancer (TNBC) is a highly aggressive disease that lacks therapeutic targets and prognostic biomarkers. Claudin-1 is a well-described tight junction protein with prognostic value in many human cancers. Aims The need for the discovery of biomarkers of TNBC disease was a major reason for this study. Claudin-1 is a tight junction protein that has shown promising results in the prognosis and management of cancer in general. In the breast, claudin-1 expression and significance have shown variable results, especially in TNBC patients. Our study assessed expression of claudin-1 in a group of TNBC patients, and correlated this expression with clinical-pathological parameters, and with the expression of β-catenin. Materials and methods Tissues from a group of 52 TNBC patients were retrieved from the archives of the community hospital. All related information including demographical, pathologic and clinical data were retrieved. Immunohistochemistry assays of a rabbit polyclonal antibody anti-human claudin-1 were applied using the avidin-biotin peroxidase methodology. Results A statistically significant majority of TNBC cases positively expressed claudin-1 (81%, χ2=13.705; p<0.001). Most TNBC cases had grade 2 β-catenin expression (77.5%; p<0.001), and positive expression for claudin-1 correlated with that of β-catenin (χ2= 23.757; p<0.001). Claudin-1 and β-catenin expressions within tumour cells shared several features including absent or weakness of membranous expression, and redistribution of both proteins to the cytoplasm of tumour cells, and in some cases to the nuclei of these cells. Claudin-1 expression also correlates with adverse survival outcomes, where only four of 20 claudin-1-positive patients who received neo-adjuvant chemotherapy (NAC) achieved pathological complete response (pCR). Conclusions The above presents a complex role of claudin-1 in TNBC patients. In this study, claudin-1 expression was associated with poor prognostic features including invasion, metastases and adverse clinical outcomes. Claudin-1 expression in TNBC correlated with the expression of β-catenin, an important oncogene and a major contributor to the epithelial mesenchymal transition (EMT) phenomenon. Overall, the above results may serve as an impetus for further mechanistic studies to assess the exact role of claudin-1 in TNBC and its possible use in the management of this subset of breast cancer.
背景 三阴性乳腺癌（TNBC）是一种侵袭性很强的疾病，缺乏治疗靶点和预后生物标志物。Claudin-1是一种在许多人类癌症中具有预后价值的紧密连接蛋白。目的 发现TNBC疾病生物标志物的需求是本研究的主要原因。Claudin-1是一种紧密连接蛋白，总体上在癌症的预后和管理方面已显示出有前景的结果。在乳腺中，Claudin-1的表达和意义呈现出不同的结果，尤其是在TNBC患者中。我们的研究评估了一组TNBC患者中Claudin-1的表达，并将这种表达与临床病理参数以及β-连环蛋白的表达相关联。材料和方法 从社区医院的档案中获取了一组52例TNBC患者的组织。检索了所有相关信息，包括人口统计学、病理和临床数据。使用抗人Claudin-1兔多克隆抗体，采用抗生物素蛋白-生物素过氧化物酶方法进行免疫组织化学检测。结果 统计学上有显著多数的TNBC病例Claudin-1呈阳性表达（81%，χ2=13.705；p<0.001）。大多数TNBC病例β-连环蛋白表达为2级（77.5%；p<0.001），Claudin-1的阳性表达与β-连环蛋白的阳性表达相关（χ2=23.757；p<0.001）。肿瘤细胞内Claudin-1和β-连环蛋白的表达具有几个共同特征，包括膜表达缺失或减弱，以及这两种蛋白重新分布到肿瘤细胞的细胞质中，在某些情况下还分布到这些细胞的细胞核中。Claudin-1的表达也与不良生存结果相关，在接受新辅助化疗（NAC）的20例Claudin-1阳性患者中，只有4例达到病理完全缓解（pCR）。结论 上述情况表明Claudin-1在TNBC患者中具有复杂的作用。在本研究中，Claudin-1的表达与包括侵袭、转移和不良临床结果在内的不良预后特征相关。TNBC中Claudin-1的表达与β-连环蛋白的表达相关，β-连环蛋白是一种重要的癌基因，也是上皮-间质转化（EMT）现象的主要促成因素。总体而言，上述结果可能为进一步的机制研究提供动力，以评估Claudin-1在TNBC中的确切作用及其在这种亚型乳腺癌管理中的可能用途。
