Department of General Surgery, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
J Cell Mol Med. 2020 Nov;24(21):12726-12735. doi: 10.1111/jcmm.15856. Epub 2020 Oct 6.
CDHR5 has been reported to play key roles in carcinogenesis of various cancers, but its roles in pancreatic cancer have not been reported. The present study was designed to investigate its clinical value in pancreatic ductal adenocarcinoma (PDAC). Tissue microarray-based immunohistochemistry was performed to analyse the correlation between CDHR5 expression and clinical and pathological features of PDAC, as well as the CDHR5 expression during tumour progression. Cell function assays were performed to investigate CDHR5's effects on PDAC cells. Moreover, qRT-PCR was applied to investigate the expression of CDHR5 isoforms in PDAC cells. Expression of CDHR5 was higher on the membrane of PDAC cells. This high expression level was associated with shorter overall survival of PDAC patients and was identified as an independent prognostic factor for overall survival by multivariate Cox regression analysis. In addition, expression level of CDHR5 presented an increased trend in the occurrence and progression of PDAC. Cell experiment suggested that CDHR5 could notably promote invasion and migration of PDAC cells. Moreover, analysis of CDHR5 isoforms indicated CDHR5-L was the major isoform expressed in PDAC cell lines. CDHR5 appears to be a promising and novel prognostic factor for PDAC, and its promotion in PDAC metastasis might be ascribed to the isoform CDHR5-L.
CDHR5 已被报道在多种癌症的发生发展中发挥关键作用,但它在胰腺癌中的作用尚未被报道。本研究旨在探讨其在胰腺导管腺癌(PDAC)中的临床价值。通过组织微阵列免疫组织化学分析,研究了 CDHR5 表达与 PDAC 的临床和病理特征之间的相关性,以及在肿瘤进展过程中 CDHR5 的表达情况。通过细胞功能测定研究了 CDHR5 对 PDAC 细胞的影响。此外,应用 qRT-PCR 研究了 PDAC 细胞中 CDHR5 异构体的表达。CDHR5 在 PDAC 细胞的膜上表达较高。这种高表达水平与 PDAC 患者的总生存期较短相关,并通过多变量 Cox 回归分析确定为总生存期的独立预后因素。此外,CDHR5 的表达水平在 PDAC 的发生和进展中呈现出增加的趋势。细胞实验表明,CDHR5 可显著促进 PDAC 细胞的侵袭和迁移。此外,对 CDHR5 异构体的分析表明,CDHR5-L 是 PDAC 细胞系中主要表达的异构体。CDHR5 似乎是 PDAC 的一个有前途的新型预后因素,其在 PDAC 转移中的促进作用可能归因于 CDHR5-L 异构体。