SOX12与肝细胞癌患者不良预后和免疫浸润的相关性研究
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湖北省卫生健康科研基金(WJ2021M217);江汉大学高层次人才科研启动基金(20200010)


SOX12 is associated with poor prognosis and immune infiltration in hepatocellular carcinoma patients
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    摘要:

    目的:通过加权基因共表达网络(weighted gene co-expression network analysis,WGCNA)与最小绝对收缩和选择算法(least absolute shrinkage and selection operator,LASSO)考察转录因子SOX12在肝细胞癌(hepatocellular carcinoma,HCC)发生发展中免疫浸润相关的预后价值。方法:利用基因表达(Gene Expression Omnibus,GEO)和肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)数据库,采用Kaplan-Meier(K-M)生存曲线和单因素、多因素Cox回归分析SOX12基因表达在HCC中的临床价值。利用ESTIMATE和CIBERSORT算法研究SOX12基因表达与肿瘤免疫微环境的相关性。运用WGCNA和LASSO算法建立风险预后模型,进一步评估高低风险组中SOX12基因表达对HCC患病基因突变的影响。结果:在HCC肿瘤组织中,SOX12的表达显著升高,和年龄、性别、肿瘤等级、疾病分期有关,且与患者生存预后显著相关。在风险预后模型中,高风险组比低风险组的总生存率差。风险预后模型具有显著的预后预测效果,其1年、3年和5年的曲线下面积(area under curve,AUC)分别为0.823、0.811和0.824。高SOX12表达组中TP53基因突变比例(40%)明显高于低SOX12表达组(25%),表明高低风险组中高低SOX12表达影响HCC患病基因突变的频率。结论:SOX12表达与HCC的免疫浸润和患病基因突变相关,提示其可能成为HCC患者预后评估的潜在靶标。

    Abstract:

    Objective:The weighted gene co-expression network(WGCNA)and least absolute shrinkage and selection operator(LASSO)were used to investigate the prognostic value of transcription factor SOX12 in the occurrence and development of hepatocellular carcinoma(HCC). Methods:Using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)corresponding information,Kaplan-Meier(K-M)survival curve and single factor,multivariate Cox regression were used to analyze the clinical value of SOX12 gene expression in HCC. ESTIMATE and CIBERSORT algorithms were used to study the correlation between SOX12 gene expression and tumor immune microenvironment. The WGCNA and LASSO algorithms were used to establish a risk prognosis model to further evaluate the effect of SOX12 gene expression in the high and low risk groups on the mutations of HCC genes. Results:In HCC tumor tissues,the expression of SOX12 was significantly increased,which was related to age,gender,tumor grade,disease stage,and was significantly related to the survival and prognosis of patients. In the risk prognosis model of immune-related genes(IRGs) showed that the overall survival rate of the high-risk group was worse than that of the low-risk group. The risk prognosis model had a significant prognostic prediction effect,and its 1-year,3-year and 5-year AUCs were 0.823,0.811 and 0.824,respectively. The proportion of TP53 gene mutations in the high SOX12 expression group(40%)was significantly higher than that in the low SOX12 expression group(25%). The results indicated that the high and low SOX12 expression in the high and low risk groups affects the frequency of HCC genetic mutations. Conclusion:The expression of SOX12 is associated with HCC immune infiltration and disease gene mutations,suggesting that it may become a potential target for prognostic evaluation of HCC patients.

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方 萌,池晴佳,赵 晗,郭 敬,刘宇炜. SOX12与肝细胞癌患者不良预后和免疫浸润的相关性研究[J].南京医科大学学报(自然科学版),2021,(8):1141-1150

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  • 收稿日期:2021-03-23
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  • 在线发布日期: 2021-08-30
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