皮肤黑色素瘤中SKA3表达及潜在分子机制分析

SKA3 expression and its potential molecular mechanism in skin cutaneous melanoma

目的探讨纺锤体与着丝粒相关蛋白3(spindle and kinetochore associated complex subunit 3,SKA3)在皮肤黑色素瘤(skin cutaneous melanoma,SKCM)中的表达及其潜在分子机制。方法GEO、GTEx和GEPIA等数据库分析SKA3 mRNA在SKCM和正常皮肤组织中的表达及其对预后的影响。采用免疫组化SP法检测SKA3蛋白在43例SKCM组织和配对正常皮肤组织中的表达,并分析SKA3表达与SKCM临床病理特征的相关性。利用Linkedomics数据网站筛选SKA3基因的共表达基因。DAVID数据库对SKA3基因的共表达基因进行基因富集分析和通路富集分析。String数据库分析SKA3蛋白上下游的关系。TISIDB软件探究SKA3表达与肿瘤免疫细胞浸润的关系。结果GEO、GTEx和GEPIA等数据库分析结果显示,SKA3 mRNA在SKCM组织中表达上调(P<0.05),且SKA3 mRNA表达与SKCM患者的总生存期(P=0.035)和无瘤生存期(P=0.018)有关。免疫组化结果显示,SKA3蛋白在SKCM组织中的阳性率(55.81%)显著高于正常皮肤组织(2.33%)(P<0.001)。SKA3蛋白表达与患者年龄、淋巴结转移、脉管内癌栓相关(P均<0.05),与患者性别、肿物直径、Breslow厚度、Clark分期、神经侵犯均无相关性(P>0.05)。SKA3表达与活化CD4+T细胞呈正相关,与不成熟B细胞、肥大细胞、Ⅰ型辅助T细胞以及效应记忆CD8+T细胞呈负相关。结论SKA3基因高表达可能促进SKCM的发生,并且与患者预后显著相关,有望成为SKCM治疗的潜在靶点。

Purpose To analyze the expression and potential significance of spindle and kinetochore associated complex subunit 3(SKA3)gene in skin cutaneous melanoma(SKCM).Methods The expression of SKA3 gene in SKCM and normal tissues and and its effect on patients’prognosis were analyzed based on GEO,GTEx and GEPIA database data,and its protein was measured by immunohistochemical staining in 43 cases of SKCM and matched normal tissues;the association of SKA3 expression and clinicopathological features of SKCM was analyzed by Chi-square test.The co-expression genes related to SKA3 gene in SKCM were screened through Linkedomics website data,and then the co-expression genes were analyzed by GO and KEGG pathway enrichment in DAVID database.String database was used to analyze the protein-protein interaction and upstream and downstream of SKA3 protein.TISIDB software was used to carried out the relationship analysis between SKA3 expression and the infiltration of tumor immune cells.Results The mRNA of SKA3 was up-regulated in SKCM(P<0.05)based on GEO,GTEx and GEPIA database data.Furthermore,the expression of SKA3 was associated with the overall survival(P=0.035)and disease-free surviva(P=0.018)of patients with SKCM.The positive rate of SKA3 protein in SKCM was 55.81%,and it was significantly higher than that in normal tissues(2.33)(P<0.001).The expression of SKA3 protein was correlated with the patient's age(P<0.05),lymph node metastasis(P<0.05),intravascular carcinoma thrombosis(P<0.05),and no significantly correlated with sex,tumor size,Breslow thickness,Clark stage,and nerve invasion(P>0.05).The expression of SKA3 gene was positively correlated with activated CD4+T cells,and negatively correlated with immature B cells,mast cells,type 1 helper T cells and effector memory CD8+T cells.Conclusion SKA3 is highly expressed in SKCM,which is involved in the pathogenesis of tumor,and is significantly related to the prognosis of patients.It may be used as a potential target for SKCM treatment.