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血管生成素-2 在胰腺癌预后中可能具有双重作用。

The possible dual role of Ang-2 in the prognosis of pancreatic cancer.

机构信息

Department of Surgery, Helsinki University Hospital, Helsinki, Finland.

Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

出版信息

Sci Rep. 2023 Oct 31;13(1):18725. doi: 10.1038/s41598-023-45194-0.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, which raises the intratumoral interstitial pressure leading to vascular collapse and hypoxia, inducing angiogenesis. Vascular growth factors, such as vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), increase in PDAC. A high VEGF and a high circulating Ang-2 associate with shorter survival in PDAC. In addition to the circulatory Ang-2, PDAC endothelial and epithelial cells express Ang-2. No correlation between tumor epithelial nor endothelial cell Ang-2 expression and survival has been published. We aimed to examine Ang-2 expression and survival. This study comprised PDAC surgical patients at Helsinki University Hospital in 2000-2013. Ang-2 immunohistochemistry staining was completed on 168 PDAC patient samples. Circulating Ang-2 levels were measured using ELISA in the sera of 196 patients. Ang-2 levels were assessed against clinical data and patient outcomes. A low tumor epithelial Ang-2 expression predicted shorter disease-specific survival (DSS) compared with a high expression (p = 0.003). A high serum Ang-2 associated with shorter DSS compared with a low circulating Ang-2 (p = 0.016). Ang-2 seemingly plays a dual role in PDAC survival. Further studies are needed to determine the mechanisms causing tumor cell Ang-2 expression and its positive association with survival.

摘要

胰腺导管腺癌(PDAC)的特征是致密的纤维母细胞性基质,这会导致肿瘤内间质压力升高,导致血管塌陷和缺氧,从而诱导血管生成。血管生长因子,如血管内皮生长因子(VEGF)和血管生成素-2(Ang-2),在 PDAC 中增加。高 VEGF 和高循环 Ang-2 与 PDAC 患者的生存时间较短相关。除了循环中的 Ang-2,PDAC 内皮细胞和上皮细胞也表达 Ang-2。肿瘤上皮细胞和内皮细胞 Ang-2 表达与生存之间没有相关性尚未发表。我们旨在研究 Ang-2 表达与生存之间的关系。本研究纳入了 2000 年至 2013 年在赫尔辛基大学医院接受手术治疗的 PDAC 患者。对 168 例 PDAC 患者样本进行了 Ang-2 免疫组化染色。使用 ELISA 法测量了 196 例患者血清中的循环 Ang-2 水平。评估了 Ang-2 水平与临床数据和患者预后之间的关系。与高表达相比,肿瘤上皮细胞 Ang-2 低表达预示着疾病特异性生存(DSS)更短(p=0.003)。与低循环 Ang-2 相比,高血清 Ang-2 与较短的 DSS 相关(p=0.016)。Ang-2 在 PDAC 生存中似乎发挥双重作用。需要进一步的研究来确定导致肿瘤细胞 Ang-2 表达及其与生存的正相关的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7520/10618172/cf93319dc1be/41598_2023_45194_Fig1_HTML.jpg

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