Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 22185, Lund, Sweden.
Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland.
Sci Rep. 2020 Jun 25;10(1):10373. doi: 10.1038/s41598-020-67187-z.
The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n = 175) and (Cohort 2, n = 189). The effect of TGF-β-induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.
壶腹周围腺癌的预后仍然很差，治疗选择有限。足细胞蛋白样蛋白（PODXL）是一种抗黏附蛋白，其高表达已被证明在许多恶性肿瘤中预示着不良预后。在结直肠癌中，已经观察到 PODXL 与表皮生长因子受体（EGFR）之间存在相关性和不良预后协同作用。在这里，我们研究了这是否也适用于壶腹周围腺癌。我们分析了来自两个患者队列的组织微阵列中 PODXL 和 EGFR 的免疫组织化学表达；（队列 1，n = 175）和（队列 2，n = 189）。在体外研究了 TGF-β诱导的 PODXL 和 EGFR 的表达以及 siRNA 介导的敲低对胰腺癌细胞（PANC-1）的影响。我们发现这些癌症中 PODXL 与 EGFR 之间存在相关性，并且对生存有协同的不良影响。此外，沉默胰腺癌细胞中的 PODXL 导致 EGFR 的下调，但反之则不然。因此，这些发现表明 PODXL 和 EGFR 之间存在功能联系，并且作为生物标志物具有潜在的联合应用价值，可能改善患者分层。进一步研究检查这些观察结果背后的机制基础可能为受这些特别侵袭性癌症影响的患者亚组开辟新的靶向治疗选择途径。
