Ahypoxia-related signature enhances the prediction of the prognosis in hepatocellular carcinoma patients and correlates with sorafenib treatment response.
Ahypoxia-related signature enhances the prediction of the prognosis in hepatocellular carcinoma patients and correlates with sorafenib treatment response.
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发表时间：
2020
影响因子：
2.2
通讯作者：
Hongye Jiang;G. Ning;Yensheng Wang;Wei-Biao Lv
中科院分区：
文献类型：
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作者：
Hongye Jiang;G. Ning;Yensheng Wang;Wei-Biao Lv
肝细胞癌（HCC）是导致癌症死亡的主要原因之一，是肝脏的原发性恶性肿瘤。肿瘤缺氧是参与肿瘤发生的应激因素，显著增加HCC的侵袭性。本文系统分析了84个缺氧相关基因在肝癌组织中的表达谱及其预后价值。从TCGA、GSE 14520、GSE 109211和ICGC下载84个缺氧相关基因的mRNA表达和肝癌患者的临床参数。在84个缺氧相关基因的基础上，对无监督类进行一致性聚类分析。使用单变量和LASSO分析来开发风险特征。APEX 1、ATR、CTSA、DNAJC 5、ENO1、EPO、HMOX 1、LDHA、NDRG 1和PER 1的表达与HCC患者的OS和DFS显著相关。我们通过风险特征将HCC患者分为高风险组和低风险组。高危组患者的OS和DFS较短，而低危组患者的OS和DFS较长。在预测OS和DFS方面，风险特征比TNM分期具有更好的预测效率。此外，巨噬细胞M0细胞，调节性T细胞和中性粒细胞被发现在高危组患者中显著富集。接下来，我们验证了GSE 14520和ICGC HCC队列中风险特征的区分和预后价值。最后，在GSE 109211队列的索拉非尼治疗应答者中发现显著较低的风险评分，预测索拉非尼治疗应答的AUC为0.881。总之，10个缺氧相关基因表达的风险特征改善了HCC的预后预测，并与索拉非尼治疗反应相关。
Hepatocellular carcinoma (HCC) is one of the leading cancer death and is the primary malignancy of the liver. Tumor hypoxia is the stressor that is involved in tumorigenesis and significantly increased the aggressiveness of HCC. Here, we systematically analyzed the expression profiles and prognostic values of 84 hypoxia associated genes in HCC. mRNA expression of 84 hypoxia associated genes and clinical parameters of HCC patients were downloaded from TCGA, GSE14520, GSE109211 and ICGC. Consensus clustering analysis was performed for unsupervised classes on the basis of 84 hypoxia associated genes. Univariate and LASSO analysis were used to develop the risk signature. A risk signature was developed, including the expression of APEX1, ATR, CTSA, DNAJC5, ENO1, EPO, HMOX1, LDHA, NDRG1, and PER1, and found to be significantly related with OS and DFS of HCC patients. We stratified HCC patients into the high-risk group and low-risk group by means of the risk signature. Patients of high-risk group had shorter OS and DFS, while that of the low-risk group had longer OS and DFS. The risk signature showed better predictive efficiency than the TNM staging in predicting OS and DFS. Also, macrophage M0 cells, regulatory T cells, and neutrophils were found to be significantly enriched in patients of high-risk group. Next, we validated the discrimination and prognostic value of the risk signature in GSE14520 and the ICGC HCC cohort. Finally, significantly lower risk scores were found in sorafenib treatment responders of GSE109211 cohort, and the AUC for predicting sorafenib treatment response was 0.881. In conclusion, a risk signature developed with the expression of 10 hypoxia associated genes improved the prognosis prediction of HCC and correlated with sorafenib treatment response.