Ormanns Steffen, Altendorf-Hofmann Annelore, Jackstadt Rene, Horst David, Assmann Gerald, Zhao Yue, Bruns Christiane, Kirchner Thomas, Knösel Thomas
Institute of Pathology, Ludwig-Maximilians-University, Thalkirchner Strasse 36, Munich 80337, Germany.
Department of General, Visceral and Vascular Surgery, Jena University Hospital, Erlanger Allee 101, Jena 07747, Germany.
Br J Cancer. 2015 Nov 17;113(10):1460-6. doi: 10.1038/bjc.2015.362. Epub 2015 Oct 15.
Frequent disease relapse and a lack of effective therapies result in a very poor outcome in pancreatic ductal adenocarcinoma (PDAC) patients. Thus, identification of prognostic biomarkers and possible therapeutic targets is essential. Besides their function in cell-cell adhesion, desmogleins may play a role in tumour progression and invasion that has not been investigated in PDAC to date. This study evaluated desmoglein expression as a biomarker in PDAC.
Using immunohistochemistry, we examined desmoglein 1 (DSG1), desmoglein 2 (DSG2) and desmoglein 3 (DSG3) expression in the tumour tissue of 165 resected PDAC cases. Expression levels were correlated to the patients' clinicopathological parameters and postoperative survival times. We confirmed these results in two independent gene expression data sets.
A total of 36% of the tumours showed high DSG3 expression that correlated significantly with shorter patient survival (P=0.011) and poor tumour differentiation (P<0.001), whereas no such association was detected for DSG1 or DSG2. In RNA-Seq data and in microarray expression data, high DSG3 expression correlated significantly with poor survival (P=0.000356 and P=0.00499).
We identify DSG3 as a negative prognostic biomarker in resected PDAC, as high DSG3 expression is associated with poor overall survival and poor tumour-specific survival. These findings suggest DSG3 and its downstream signalling pathways as possible therapeutic targets in DSG3-expressing PDAC.
胰腺导管腺癌（PDAC）患者疾病频繁复发且缺乏有效治疗方法，导致预后极差。因此，识别预后生物标志物和可能的治疗靶点至关重要。除了在细胞间黏附中的作用外，桥粒芯糖蛋白可能在肿瘤进展和侵袭中发挥作用，而迄今为止在PDAC中尚未对此进行研究。本研究评估了桥粒芯糖蛋白表达作为PDAC中的一种生物标志物。
我们采用免疫组织化学方法，检测了165例手术切除的PDAC病例肿瘤组织中桥粒芯糖蛋白1（DSG1）、桥粒芯糖蛋白2（DSG2）和桥粒芯糖蛋白3（DSG3）的表达。表达水平与患者的临床病理参数及术后生存时间相关。我们在两个独立的基因表达数据集中证实了这些结果。
总共36%的肿瘤显示高DSG3表达，这与患者较短的生存期（P=0.011）和较差的肿瘤分化（P<0.001）显著相关，而未检测到DSG1或DSG2有此类关联。在RNA测序数据和微阵列表达数据中，高DSG3表达与较差的生存率显著相关（P=0.000356和P=0.00499）。
我们将DSG3确定为手术切除的PDAC中的一种负面预后生物标志物，因为高DSG3表达与总体生存率低和肿瘤特异性生存率低相关。这些发现表明DSG3及其下游信号通路可能是表达DSG3的PDAC的治疗靶点。
