Alattar Mohamed, Omo Alfred, Elsharawy Mamdouh, Li Jun
Department of Cardiothoracic Surgery, Zagazig University, Zagazig, Egypt.
Eur J Cardiothorac Surg. 2014 Mar;45(3):514-20. doi: 10.1093/ejcts/ezt380. Epub 2013 Aug 16.
The development of new therapeutic targets is needed to change the current low survival rates of cancer of the oesophagus. In some clinical trials, angiogenic inhibitors, including those targeting the vascular endothelial growth factor (VEGF) and its receptors, have proven efficacious. In concert with this, neuropilin-1 (NRP1), a coreceptor for VEGF, is expressed by many tumours and may be related to their progression. This study aimed to assess the expression and prognostic value of fNRP1 in primary squamous cell carcinoma (SCC) of the oesophagus.
The expression of NRP1 receptors was assessed in 60 samples of resected oesophageal SCC and adjacent normal mucosa by western blotting, immunostaining and real-time quantitative PCR (qPCR). Furthermore, the relationship between NRP1 and the clinicopathological parameters was investigated.
NRP1 staining was limited within normal tissues of the oesophagus, while it was prominent in tumour cells and vasculature. Overexpression of NRP1 receptors (3.6 ± 0.48-folds) was apparent in 81.7% specimens (n = 60, P = 0.0001). qPCR consistently revealed parallel NRP1-mRNA overexpression (3.7 ± 3.7-folds) (n = 16, P = 0.02). A higher molecular weight-modified NRP1 (mNRP1) species was identified in a large proportion of the tumour specimens (85%), accounting for 71.51 ± 20.6% of their total NRP1. Overexpression of tumour NRP1 was positively correlated with deeper invasion into the oesophageal wall (P = 0.05) though mNRP1-positive tumour populations were significantly associated with less lymph node metastasis (P = 0.036) and better prognostic tumour-node-metastasis stage (P = 0.037) than mNRP1 negative tumours.
NRP1 overexpression in oesophageal SCC may contribute to local tumour invasiveness but the presence of the mNRP1 subtype correlates with less lymph node metastasis and better prognostic stage, suggesting that the balance between modified and unmodified NRP1 might be important for determining invasion potential.
需要开发新的治疗靶点来改变目前食管癌较低的生存率。在一些临床试验中，包括那些靶向血管内皮生长因子（VEGF）及其受体的血管生成抑制剂已被证明有效。与此一致的是，作为VEGF共受体的神经纤毛蛋白-1（NRP1）在许多肿瘤中表达，可能与其进展有关。本研究旨在评估fNRP1在原发性食管鳞状细胞癌（SCC）中的表达及预后价值。
通过蛋白质免疫印迹、免疫染色和实时定量PCR（qPCR）检测60例手术切除的食管SCC标本及癌旁正常黏膜中NRP1受体的表达。此外，研究NRP1与临床病理参数之间的关系。
NRP1染色在食管正常组织中局限，而在肿瘤细胞和脉管系统中显著。81.7%的标本（n = 60，P = 0.0001）中NRP1受体明显过表达（3.6±0.48倍）。qPCR始终显示NRP1 mRNA平行过表达（3.7±3.7倍）（n = 16，P = 0.02）。在大部分肿瘤标本（85%）中鉴定出一种分子量更高的修饰型NRP1（mNRP1），占其总NRP1的71.51±20.6%。肿瘤NRP1过表达与食管壁深层浸润呈正相关（P = 0.05），不过与mNRP1阴性肿瘤相比，mNRP1阳性肿瘤群体与较少的淋巴结转移（P = 0.036）及更好的预后肿瘤-淋巴结-转移分期（P = 0.037）显著相关。
食管SCC中NRP过表达可能促进局部肿瘤侵袭，但mNRP1亚型的存在与较少的淋巴结转移及更好的预后分期相关联，这表明修饰型和未修饰型NRP1之间的平衡对于确定侵袭潜能可能很重要。
