Epithelial ovarian cancer is aggressive and causes high mortality among women worldwide. Members of the plakin family are essential to maintain cytoskeletal integrity and key cellular processes. In this study we characterised the expression of plakins, particularly plectin (PLEC), periplakin (PPL), envoplakin (EVPL), and EMT-related proteins by immunohistochemistry in n = 48 patients’ samples to evaluate a potential correlation of plakin expression with EMT as EOC progresses. These tissue plakin and EMT expression analyses were further evaluated by in vitro cell line expression and correlated with the expression of these molecules using publicly available datasets such as Cancer Genome Atlas (TCGA) and Clinical Proteome Tumour Analysis Consortium (CPTAC) datasets. We demonstrate that the expression of PPL and PLEC plakins is decreased in high-grade compared to low-grade EOCs with mixed EMT marker protein expression. This is supported by the correlation of high PPL and PLEC expression with an epithelial rather than mesenchymal phenotype. Our data suggest a partial loss of plakin expression as EOC tumours progress. This may impact the connections of plakins with membrane-bound receptors, which impede the downstream signalling required for the initiation of EMT as the tumours progress.
上皮性卵巢癌具有侵袭性,在全球范围内导致女性高死亡率。斑蛋白家族成员对维持细胞骨架完整性和关键细胞过程至关重要。本研究通过免疫组织化学方法对48例患者样本中斑蛋白(特别是网蛋白PLEC、周斑蛋白PPL、包斑蛋白EVPL)及上皮-间质转化相关蛋白的表达特征进行分析,以评估斑蛋白表达与上皮性卵巢癌进展过程中上皮-间质转化的潜在相关性。通过体外细胞系表达实验进一步验证这些组织斑蛋白及上皮-间质转化表达分析结果,并利用癌症基因组图谱和临床蛋白质组肿瘤分析联盟等公开数据集与这些分子的表达进行关联分析。研究发现,与低级别上皮性卵巢癌相比,高级别肿瘤中PPL和PLEC斑蛋白表达降低,同时伴有混合型上皮-间质转化标志蛋白表达。高表达PPL和PLEC与上皮表型而非间质表型相关的证据支持这一发现。数据表明,随着上皮性卵巢癌进展,斑蛋白表达出现部分缺失。这可能影响斑蛋白与膜结合受体的连接,从而在肿瘤进展过程中阻碍启动上皮-间质转化所需的下游信号传导。