骨肉瘤中EMT相关基因的来源及与患者生存预后的关系分析

Analysis of the source of EMT-related genes in osteosarcoma and its relationship with survival prognosis of patients

目的研究骨肉瘤中上皮间质转化(EMT)相关基因的来源及与患者生存预后的关系。方法从Gene Expression Omnibus数据库中获得3个独立的微阵列数据集(GSE36001、GSE39055和GSE16091)。GSE39055和GSE16091用于探讨骨肉瘤EMT、免疫活性、基质活性和肿瘤纯度间的相关性;GSE39055的总生存率和无病生存率数据用于生存分析。通过GSE36001和该院5例骨肉瘤标本、5例基质标本验证骨肉瘤中EMT相关基因表达的关键来源。结果GSE39055和GSE16091中,EMT评分与免疫评分、基质评分均呈正相关(P<0.05),与肿瘤纯度均呈负相关(P<0.05);肿瘤纯度与免疫评分、基质评分均呈负相关(P<0.05)。GSE39055中,高EMT评分是骨肉瘤患者总生存率、无病生存率下降的危险因素(HR=4.977,P=0.003;HR=4.308,P=0.010)。GSE36001中,骨肉瘤标本EMT相关基因表达水平高于基质细胞基因(P<0.05);骨肉瘤标本和基质标本之间EMT相关基因的倍数变化(FC)高于基质细胞基因(P<0.05)。该院5例骨肉瘤标本中EMT相关基因表达水平高于基质细胞基因(P<0.05);5例基质标本中基质细胞基因表达水平高于EMT相关基因(P<0.05);骨肉瘤标本和基质标本之间EMT相关基因的FC高于基质细胞基因(P<0.05)。结论骨肉瘤中EMT、免疫活性、基质活性和肿瘤纯度之间存在相关性;EMT相关基因的表达与骨肉瘤患者的生存预后密切相关;基质细胞是骨肉瘤中EMT相关基因表达的关键来源。

Objective To study the source of epithelial-mesenchymal transition(EMT)-related genes in osteosarcoma and its relationship with survival prognosis of patients.Methods Three independent microarray data sets(GSE36001,GSE39055 and GSE16091)were obtained from the Gene Expression Omnibus database.GSE39055 and GSE16091 were used to explore the correlation between osteosarcoma EMT,immune activity,matrix activity and tumor purity.The overall survival rate and disease-free survival rate data of GSE39055 were used for survival analysis.The key source of EMT-related genes expression in osteosarcoma was verified by GSE36001,5 osteosarcoma specimens and 5 stromal specimens from the hospital.Results In GSE39055 and GSE16091,EMT score was positively correlated with immune score and matrix score(P<0.05),and negatively correlated with tumor purity(P<0.05);tumor purity was negatively correlated with immune score and matrix score(P<0.05).In GSE39055,high EMT score was a risk factor for decreased overall survival and disease-free survival in patients with osteosarcoma(HR=4.977,P=0.003;HR=4.308,P=0.010).In GSE36001,the expression level of EMT-related genes in osteosarcoma specimens was higher than that of stromal cell genes(P<0.05);the fold change(FC)of EMT-related genes between osteosarcoma specimens and stromal specimens was higher than that of stromal cell genes(P<0.05).The expression level of EMT-related genes in 5 osteosarcoma specimens in the hospital was higher than that of stromal cell genes(P<0.05);the expression level of stromal cells gene in 5 stromal specimens was higher than that of EMT-related genes(P<0.05);the FC of EMT-related genes between osteosarcoma specimens and stromal specimens was higher than that of stromal cell genes(P<0.05).Conclusion There is a correlation between EMT,immune activity,matrix activity and tumor purity in osteosarcoma.The expression of EMT-related genes is closely related to the survival prognosis of patients with osteosarcoma.Stromal cells are the key source of EMT-related genes expression in osteosarcoma.