Shp2在三阴乳腺癌中表达及对癌细胞干性调控作用研究

Expression of Shp2 in triple-negative breast cancer and its regulation on tumor stem cells

目的探讨Shp2在三阴乳腺癌(TNBC)中表达及对癌细胞干性的调控作用。方法选取78例乳腺癌患者肿瘤组织进行Shp2表达水平检测。在基因、蛋白及组织学水平上分析TNBC样本与非TNBC样本Shp2的表达情况,并将Shp2的表达与TNBC患者的临床病理特征及复发、生存期等随访信息进行统计学分析。以TNBC细胞系MDA-MB-231和BT-20为细胞模型,通过慢病毒感染法建立Shp2高、低表达TNBC细胞系及其对照细胞系,进行低粘附悬浮培养,观察TNBC细胞在低粘附情况下成球数量的改变,体外分析Shp2对TNBC细胞干性的调控。结果 TNBC组织中Shp2的表达显著高于非TNBC组织(P<0.05);乳腺癌组织中Shp2表达高于癌旁组织(P<0.05)。乳腺癌组织中Shp2高表达组5年总体存活率与低表达组比较,差异有统计学意义(P<0.05)。乳腺癌组织中Shp2表达越高,预后越差。成球实验中,Shp2高表达的TNBC细胞系形成了更多、更大的微球。结论 Shp2可能通过调控TNBC干细胞的自我更新影响TNBC的复发转移和化疗耐药。

Objective To investigate the expression of Shp2 in triple-negative breast cancer(TNBC)and its regulation on TNBC stem cells.Methods Shp2 expression level was detected in 78 breast cancer patients.The expression of Shp2 in TNBC samples and non-TNBC samples was analyzed at the level of gene,protein and histology,and the expression of Shp2 was statistically analyzed in relation to the clinicopathological characteristics,recurrence,survival and other follow-up information of TNBC patients.TNBC cell lines MDA-MB-231 and BT-20 were used as cell models to establish TNBC cell lines with high and low expression of Shp2 and their control cell by lentivirus infection.The changes in pellet formation number of TNBC cells were observed in low-adhesion suspension culture,and the regulation of Shp2 on TNBC stem cell was analyzed in vitro.Results The expression of SHP2 in TNBC tissues was significantly higher than that in non-TNBC tissues(P<0.05);and the expression in breast cancer tissues was higher than that in adjacent tissues(P<0.05).The 5-year overall survival rate was significantly different between those with high SHP2 expression and those with low expression in breast cancer tissues(P<0.05).The higher the expression of SHP2 in breast cancer tissues,the worse the prognosis was.In the spheroidal experiment,the SHP2 overexpressing TNBC cell formed more and larger microspheres,and SHP2 may affect the self-renewal ability of the TNBC stem cells.Conclusion SHP2 may affect the recurrence and metastasis of TNBC and chemoresistance by regulating the self-renewal of TNBC stem cells.