肿瘤标志物及EMT通路表达水平对黑色素瘤预后的影响

Effect of tumor markers and EMT pathway expression level on prognosis of melanoma

目的探讨上皮-间充质转化(EMT)通路对黑色素瘤患者预后的影响及黑色素瘤常见肿瘤标志物与EMT通路的相关性,为临床识别和随访高转移风险的黑色素瘤患者提供新思路。方法从TCGA数据库中获得461例黑色素瘤患者的转录及临床数据,通过GSVA包对每个样本的表达进行非参数的无监督分析,得到EMT通路的表达评分并分为低和高两组,使用Survival包进行生存分析。随后对肿瘤标志物的mRNA和EMT通路表达水平进行Spearman相关性分析,并根据年龄、性别和肿瘤分期进行亚组分析。进一步从TCGA数据库中下载黑色素瘤患者肿瘤标志物的蛋白表达水平,同样进行Spearman相关性分析,从mRNA和蛋白表达水平2个角度探讨常见肿瘤标志物与EMT通路的相关性。最后将上述肿瘤标志物、EMT通路表达水平和临床特征纳入多因素分析以明确对黑色素瘤预后的影响。结果EMT通路的高表达预示黑色素瘤患者的不良预后。黑色素瘤肿瘤标志物PMEL、MLANA、TYR和MITF的mRNA表达水平与EMT通路呈负相关(P<0.05),MKI67的mRNA表达水平与EMT通路呈正相关(P<0.05)。肿瘤标志物与EMT通路相关性的亚组分析结果与总样本中所得结果基本一致。肿瘤标志物PMEL高表达和EMT相关通路低表达时预示良好预后,EMT相关通路低表达时MLANA、MKI67低表达预示良好预后(P<0.05)。PMEL、MLANA和MITF的蛋白表达水平与EMT通路的表达呈负相关(P<0.05)。PMEL、年龄和病理分期是影响黑色素瘤预后的独立危险因素(P<0.05)。结论黑色素瘤的常见肿瘤标志物PMEL、MLANA和MITF较低表达可能与EMT通路的高表达相关;EMT相关通路低时,PMEL与MLANA高表达、MKI67低表达预示良好预后,随访中应给予一定程度重视。

Objective To explore the effect of EMT pathway on the prognosis of the patients with melanoma and the correlation between common tumor markers and EMT pathway to provide the new ideas for clinical identification and follow-up of melanoma patients with high risk of metastasis.Methods The transcriptional and clinical data of 461 melanoma patients were obtained from the TCGA database.The expression of each sample was analyzed by GSVA package with non-parametric unsupervised analysis,and the expression score of EMT pathway was obtained and divided into the low and high groups.The survival package was used for conducting the survival analysis.Then the mRNA and EMT pathway expression levels of tumor markers conducted the Spearman correlation analysis,moreover the subgroup analysis was performed according to age,sex and tumor stage.The protein expression levels of tumor markers in melanoma patients were further downloaded from the TCGA database,and the correlation analysis was also conducted to explore the correlation between the common tumor markers and EMT pathways from two perspectives of mRNA and protein expression levels.Finally,the above tumor markers,EMT pathway expression levels and clinical features were included in a multi-factor analysis to determine their impact on melanoma prognosis.Results The high expression of EMT pathway predicted the poor prognosis of melanoma patients.The mRNA expression levels of melanoma tumor markers PMEL,MLANA,TYR,and MITF were negatively correlated with the EMT pathway(P<0.05),while the mRNA expression level of MKI67 was positively correlated with the EMT pathway(P<0.05).The results of subgroup analysis of the correlation between the tumor markers and EMT pathway were basically consistent with those obtained in the total sample.High expression of tumor marker PMEL and low expression of EMT-related pathway predicted a good prognosis,while low expression of MLANA and MKI67 predicted a good prognosis when EMT-related pathway was low expression(P<0.05).The protein expression levels of PMEL,MLANA and MITF were negatively correlated with the expression of EMT pathway(P<0.05).PMEL,age and tumor stage might be the independent risk factors for melanoma prognosis.Conclusion The lower expressions of PMEL,MLANA and MITF common markers of melanoma may be related to the high expression of EMT pathway.When the EMT-related pathways are low,high expression of PMEL and MLANA and low expression of MKI67 predict a good prognosis,which should be paid a certain degree of attention to during follow-up.