Barber Alison G, Castillo-Martin Mireia, Bonal Dennis M, Rybicki Benjamin A, Christiano Angela M, Cordon-Cardo Carlos
Department of Genetics and Development, Columbia University, New York, New York, United States of America.
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
PLoS One. 2014 Jun 4;9(6):e98786. doi: 10.1371/journal.pone.0098786. eCollection 2014.
The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer.
We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance.
These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome.
Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer.
桥粒芯糖蛋白(DSGs)对于建立和维持组织完整性所需的细胞间黏附至关重要,其在表皮和毛囊中的表达已得到充分表征;然而,它们在前列腺等其他上皮组织中的表达却知之甚少。尽管在前列腺癌组织样本中已描述了经典钙黏蛋白(如E-钙黏蛋白)的下调,但桥粒芯糖蛋白的表达此前仅在前列腺癌细胞系中有报道。在本研究中,我们对正常前列腺组织中桥粒芯糖蛋白的表达进行了表征,并进一步研究了桥粒芯糖蛋白2(DSG2)的表达是否可作为诊断为原发性前列腺癌患者的潜在临床预后因素。
我们利用免疫荧光法检测了正常前列腺组织(n = 50)以及一组临床特征明确的前列腺癌患者(n = 414)中DSG2的表达。分析DSG2表达与临床病理特征及生化复发的相关性,以评估其临床意义。
这些研究表明,DSG2和DSG4在前列腺腔面细胞中特异性表达,而基底细胞中则缺乏其表达。相反,DSG1和DSG3在正常前列腺上皮中不表达。对前列腺癌中DSG2表达的进一步分析显示,该生物标志物水平降低是不良临床结局的一个重要独立标志物。
我们首次报道低DSG2表达表型是肿瘤侵袭性的一种有用预后生物标志物,可能有助于识别具有临床意义的前列腺癌患者。