婆罗双树样基因4在非小细胞肺癌中的表达及其与临床病理和分子特征的相关性

Expression of SALL4 in non-small cell lung cancer and its correlation with clinicopathological and molecular features

目的:探讨婆罗双树样基因4(SALL4)在非小细胞肺癌(NSCLC)组织中的表达及其与NSCLC临床病理因素和分子特征之间的关系。方法:选取136例NSCLC患者手术切除标本、165例晚期肺腺癌患者穿刺活检标本,采用免疫组织化学方法检测SALL4蛋白、干细胞标志物CD44、上皮间质转化(EMT)相关标志物(E-cadherin、Vimentin)和ALK蛋白(D5F3)的表达,核酸分子原位杂交技术检测Snail mRNA,利用基因突变扩增阻滞系统(ARMS)检测EGFR和KRAS基因突变。结果:癌旁组织SALL4阴性,136例手术切除原发性NSCLC组织SALL4阳性率21.3%,有淋巴结转移、UICC分期Ⅲ期、低分化的NSCLC组SALL4阳性强度均高于相应对照组(P<0.05),SALL4阳性NSCLC患者术后无进展生存率、总体生存率均低于SALL4阴性者(P<0.05)。165例晚期肺腺癌穿刺活检组织中SALL4阳性率21.8%,其中腺泡型腺癌SALL4阳性率高于其他类型,基因检测结果显示EGFR突变组SALL4阳性率高于野生型组(P<0.05);SALL4的阳性率与E-cadherin呈负相关,与Vimentin、Snail和CD44表达正相关(P<0.05)。结论:表达SALL4的NSCLC侵袭性更强,SALL4蛋白表达与上皮间质转化和EGFR突变有关,可为肺癌的侵袭、转移研究和患者的预后判断提供帮助。

Objective:To investigate the clinicopathological and molecular features of SALL4 expression in non-small cell lung cancer(NSCLC).Methods:The expression of SALL4,epithelial mesenchymal transition(EMT)markers(E-cadherin,Vimentin),CD44 and ALK(D5F3)were detected by immunohistochemistry and Snail mRNA was stedied using in situ hybridization in formalin-fixed and paraffin-embedded tissues from 301 patients with NSCLC.Amplification refractory mutation system(ARMS)was used to determin the mutation status of EGFR and KRAS.Results:SALL4 was expressed in 21.3%(29/136)NSCLC specimens from patients who under pulmonary resections,SALL4-positive NSCLCs demonstrated more frequent lymphatic metastasis,poor differentiation,advanced stage(P<0.05).Patients with SALL4-positive NSCLCs showed significantly shorter progression-free and overall survival compared to patients with SALL4-negative NSCLCs(P<0.05).SALL4 was expressed in 21.8%(36/165)biopsy specimens of advanced lung adenocarcinoma,and the expression of SALL4 in the patients who harbored EGFR mutation was much higher than wild types of EGFR(P<0.05).SALL4-positive NSCLCs were characterized by increased expression of Vimentin,Snail,CD44 and loss of E-cadherin expression(P<0.05).Conclusion:Our results suggest that SALL4 is closely related to EMT and EGFR mutation in NSCLCs.SALL4-positive NSCLCs demonstrate more aggressive biological behavior.SALL4 has the potential to serve as a prognostic marker for NSCLCs.