中文摘要：

目的：探讨非小细胞肺癌（non-small cell lung cancer,NSCLC）中DKK1影响线性程序性坏死（linearly patterned programmed cell necrosis,LPPCN）和血管生成拟态（vasculogenic mimicry,VM）的机制。方法：收集人NSCLC标本173例,H＆E染色检测LPPCN,CD31/PAS双染检测VM,免疫组织化学检测DKK1及相关蛋白表达,分析其临床病理意义及相互关系,进而裸鼠H460-DKK1移植瘤体内验证研究假设。结果：NSCLC中14.45%（25/173）存在VM,49.71%（86/173）具有LPPCN,LPPCN（＋）组25.6%（22/86）形成VM,二者均与分化差、TNM分期晚、易复发转移和预后差相关。VM（＋）组和LPPCN（＋）组DKK1均高表达,均与VE-cadherin、MMP-2、β-catenin核表达及Twist1正相关。H460-DKK1移植瘤模型证实DKK1促进VM和LPPCN及相关蛋白表达上调。结论：DKK1引起的β-catenin、Twist1表达上调可促进NSCLC中LPPCN和VM形成。

英文摘要：

Objective： To investigate the effect of DKK1 on linearly patterned programmed cell necrosis （LPPCN） and vasculogenic mimicry （VM） and the related molecular mechanism in non-small cell lung cancer （NSCLC）. Methods： A total of 173 human NSCLC specimens were collected to detect LPPCN by H ＆ E staining, detect VM with CD31/PAS double staining, and investigate DKK1 and related protein expression by immunohistochemistry. The clinical pathological significance of LPPCN, VM, and DKK1 and the correlation of them were analyzed. Human NSCLC H460-DKK1 cells were engrafed in nude mice to evaluate the influence of DKK1 up-regulation on VM and LPPCN in vivo. Results： Approximately, 14.45% （25/173） of NSCLC had VM and 49.71% （86/173） had LPPCN. 25.6% （22/86） of NSCLC cases in LPPCN -positive group formed VM. Both of VM and LPPCN were all correlated with poor differentiation, late TNM stage, easy recurrence and metastasis and poor prognosis in NSCLC. DKK1 expression in the VM-positive group and the LPPCN-positive group was higher than that in the VM-negative group and the LPPCN-negative group, respectively. DKK1, LPPCN, and VM were positively correlated with VE-cadherin, MMP-2, β-catenin nuclear expression and Twist1. H460-DKK1 transplantation tumor model confirmed that DKK1 promotes the expression of VM and LPPCN and related proteins in NSCLC. Conclusion： The increase of the β-catenin and Twist1 expression induced by DKK1 may promote the formation of LPPCN and VM in NSCLC.