Ide Shozo, Toiyama Yuji, Shimura Tadanobu, Kawamura Mikio, Yasuda Hiromi, Saigusa Susumu, Ohi Masaki, Tanaka Koji, Mohri Yasuhiko, Kusunoki Masato
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Ann Surg Oncol. 2015 Aug;22(8):2585-92. doi: 10.1245/s10434-014-4315-0. Epub 2015 Jan 7.
Angiopoietin-like protein 2 (ANGPTL2) mediates chronic inflammation. Tumor cell-derived ANGPTL2 promotes tumor invasion and angiogenesis. Overexpression of ANGPTL2 in tumor cells is associated with tumor progression and has been recognized in lung, breast, colon, and gastric cancer. However, to our knowledge the functional and clinical significance of ANGPTL2 expression has not been investigated in patients with esophageal cancer (EC).
First, in vitro assays were performed for functional analysis of ANGPTL2 using small interfering RNA. Next, ANGPTL2 expression in EC tissues (n = 71) was evaluated by immunohistochemistry (IHC in patients with EC (n = 71). Finally, serum ANGPLT2 levels from patients with EC (n = 71) and healthy controls (n = 35) were evaluated using enzyme-linked immunosorbent assay.
Knockdown of ANGPTL2 expression decreased the proliferative, invasive, and migration capacity in EC cell lines. ANGPTL2 expression in EC tissues was significantly elevated in patients with a high T stage, squamous cell carcinoma, and high TNM stage. Patients with high ANGPTL2 expression had significantly poorer overall and disease-free survival than those with low expression. Furthermore, high ANGPTL2 expression in EC tissues was an independent predictive marker for a poor prognosis. On the other hand, the serum ANGPTL2 level in patients with EC was significantly higher than that in healthy controls, and allowed for highly accurate discrimination between patients with and without EC. However, no significant association between serum ANGPTL2 levels and clinicopathological findings was observed in patients with EC.
We have demonstrated novel evidence for the clinical significance of ANGPTL2 as a biomarker in patients with EC.
血管生成素样蛋白2（ANGPTL2）介导慢性炎症。肿瘤细胞衍生的ANGPTL2促进肿瘤侵袭和血管生成。肿瘤细胞中ANGPTL2的过表达与肿瘤进展相关，并且在肺癌、乳腺癌、结肠癌和胃癌中已得到证实。然而，据我们所知，尚未对食管癌（EC）患者中ANGPTL2表达的功能和临床意义进行研究。
首先，使用小干扰RNA进行体外实验以对ANGPTL2进行功能分析。其次，通过免疫组织化学（IHC）评估71例EC组织中ANGPTL2的表达。最后，使用酶联免疫吸附测定法评估71例EC患者和35例健康对照者的血清ANGPLT2水平。
敲低ANGPTL2表达可降低EC细胞系的增殖、侵袭和迁移能力。在高T分期、鳞状细胞癌和高TNM分期的患者中，EC组织中ANGPTL2的表达显著升高。ANGPTL2高表达的患者的总生存期和无病生存期明显低于低表达患者。此外，EC组织中ANGPTL2的高表达是预后不良的独立预测指标。另一方面，EC患者的血清ANGPTL2水平显著高于健康对照者，并且能够高度准确地区分有无EC的患者。然而，在EC患者中未观察到血清ANGPTL2水平与临床病理结果之间存在显著关联。
我们已经证明了ANGPTL2作为EC患者生物标志物的临床意义的新证据。
