摘要
背景:铁是所有哺乳动物血红蛋白合成,DNA合成和能量代谢所必需的营养素。铁代谢涉及包括肝细胞癌(hepatocellular cancer, HCC)在内的多种类型的癌症。本研究的目的是确定基于铁代谢相关基因的预后模型,从而有效预测HCC患者的预后。方法:从癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库获得HCC患者的RNA微阵列和临床数据。我们通过一致性聚类分析确定了具有不同临床结果的HCC患者群,通过进行Cox回归分析筛选四种铁代谢相关基因(FLVCR1, FTL, HIF1A, HMOX1)的预后模型,利用国际癌症基因组联盟(International Cancer Genome Consortium, ICGC)数据库验证了预后模型的有效性。同时,利用Oncomine数据库、Human Protein Atlas和Kaplan Meier-plotter检测FLVCR1、FTL、HIF1A、HMOX1的表达量。结果:TCGA队列和ICGC队列中低风险评分患者的预后均优于高风险评分患者。通过OS相关的ROC曲线,预后模型显示出比其他临床病理参数更好的预测HCC患者预后的性能。结论:基于铁代谢的生存模型可能是肝细胞癌患者的独立危险因素。
Background: Iron is a nutrient essential for hemoglobin synthesis, DNA synthesis, and energy metabolism in all mammals. Iron metabolic involved in numerous types of cancers including hepatocellular cancer. In this study, we aim to identify prognostic model that based on iron metabolic-related genes that could effectively predict the prognosis for HCC patients. Methods: The RNA microarray and clinical data of HCC patients that obtained from The Cancer Genome Atlas (TCGA) database. We identify the clusters of HCC patients with different clinical outcome performed by consensus clustering analysis. Four iron metabolic-related genes (FLVCR1, FTL, HIF1A, HMOX1) were screen for prognostic model by performed the Cox regression analysis. The efficacy of prognostic model was validated by the International Cancer Genome Consortium (ICGC) database. Meantime, the expressions value of FLVCR1, FTL, HIF1A, HMOX1 was performed using Oncomine database, the Human Protein Atlas and Kaplan Meier-plotter. Result: The patients with low-risk score have better prognosis than high risk score both in TCGA cohort and ICGC cohort. The prognostic model showed well performance for predicting the prognosis of HCC patients than other clinicopathological parameters by OS-related ROC curves. Conclusion: Our survival models that based on Iron metabolic can be independent risk factors for hepatocellular carcinoma patients.
出处
《临床医学进展》
2021年第9期3969-3982,共14页
Advances in Clinical Medicine
