YWHAZ在皮肤黑色素瘤中的临床及生物学意义

Clinical and biological significance of YWHAZ in cutaneous melanoma

目的探讨YWHAZ在皮肤黑色素瘤中的表达及其临床意义,初步检测YWHAZ在皮肤黑色素瘤中的生物学功能。方法使用GEO数据库分析YWHAZ在皮肤黑色素瘤与良性痣间的表达差异,使用TCGA皮肤黑色素瘤数据集分析YWHAZ表达与皮肤黑色素瘤患者总生存之间的相关性。通过体外实验,敲减YWHAZ在皮肤黑色素瘤细胞中的表达,CCK8法检测细胞增殖,流式检测细胞凋亡,Transwell实验检测细胞迁移及侵袭能力改变。结果黑色素瘤组织中YWHAZ的平均相对表达量5.785±0.128,明显高于良性痣中YWHAZ的平均相对表达量(4.704±0.281),差异有统计学意义(t=4.023,P=0.0002);YWHAZ高表达组中位生存期(47.28个月)较低表达组(89.13个月)明显缩短(P=0.0085)。体外实验结果显示YWHAZ敲减后黑色素瘤细胞增殖减慢、凋亡细胞比例增加、迁移及侵袭能力减弱。结论YWHAZ在皮肤黑色素瘤中发挥癌基因的作用,降低YWHAZ表达水平可抑制黑色素瘤的恶性表型。

Objective The aim of the study was to analyze the expression of YWHAZ in cutaneous melanoma,and to evaluate its association with survival of melanoma patients and biological function.Methods The GEO database was used to explore the difference in YWHAZ expression between cutaneous melanoma and benign melanocytic nevi.TCGA database was used to analyze the correlation between YWHAZ expression and melanoma prognosis.The biological function of YWHAZ was investigated in vitro through gene knockdown using siRNA against YWHAZ.Cell proliferation was detected by CCK8 assay,cell apoptosis was analyzed by flow cytometry,and cell migration and invasion abilities were evaluated by Transwell assay.Results According to the GEO dataset GSE3189,we found that YWHAZ was highly expressed in cutaneous melanoma tissues(5.785±0.128)compared to benign melanocytic nevi[(4.704±0.281),t=4.023,P=0.0002].The TCGA cutaneous melanoma data showed that high YWHAZ expression was associated with a shorter overall survival.Loss-of-function studies demonstrated that YWHAZ knockdown could inhibit melanoma cell proliferation,migration,and invasion,and promote cell apoptosis.Conclusion YWHAZ is overexpressed in cutaneous melanoma and associates with a shorter overall survival.Increased expression of YWHAZ can promote the malignant biological behavior of melanoma cells.