Department of Surgery, Gachon University College of Medicine, Gil Medical Center, Incheon, Republic of Korea.
Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Sci Rep. 2019 Feb 12;9(1):1803. doi: 10.1038/s41598-018-38116-y.
Hypoxia-related gene (HRG) expression is associated with survival outcomes of colorectal cancer (CRC). Our aim was developing a nomogram predicting CRC overall survival (OS) with HRGs and clinicopathological factors. The Cancer Genome Atlas (TCGA) database was used as discovery cohort and two Gene Expression Omnibus databases (GSE39582 and GSE41258) served as validation cohorts. A genetic risk score model prognosticating OS was developed using mRNA expression level of HRGs. Nomogram predicting OS was developed using genetic risk score model and clinicopathological variables. The genetic risk score model included four HRGs (HSPA1L, PUM1, UBE2D2, and HSP27) and successfully prognosticated OS of discovery and two validation cohorts (p < 0.001 for TCGA discovery set, p < 0.003 for the GSE39582 and p = 0.042 for the GSE41258 datasets). Nomogram included genetic risk score, age, and TNM stage. Harrell's concordance indexes of the nomogram were higher than those of TNM stage alone in the discovery set (0.77 vs. 0.69, p < 0.001), GSE39582 (0.65 vs. 0.63, p < 0.001), and GSE41258 datasets (0.78 vs. 0.77, p < 0.001). Our nomogram successfully predicted OS of CRC patients. The mRNA expression level of the HRGs might be useful as an ancillary marker for prognosticating CRC outcome.
缺氧相关基因(HRG)表达与结直肠癌(CRC)的生存结局相关。我们的目的是开发一个基于 HRG 和临床病理因素预测 CRC 总生存(OS)的列线图。癌症基因组图谱(TCGA)数据库被用作发现队列,两个基因表达综合数据库(GSE39582 和 GSE41258)被用作验证队列。使用 HRG 的 mRNA 表达水平开发预测 OS 的遗传风险评分模型。使用遗传风险评分模型和临床病理变量开发预测 OS 的列线图。遗传风险评分模型包括四个 HRGs(HSPA1L、PUM1、UBE2D2 和 HSP27),并成功预测了发现队列和两个验证队列的 OS(TCGA 发现集的 p < 0.001,GSE39582 的 p < 0.003,GSE41258 的 p = 0.042)。列线图包括遗传风险评分、年龄和 TNM 分期。在发现集(0.77 与 0.69,p < 0.001)、GSE39582(0.65 与 0.63,p < 0.001)和 GSE41258 数据集中,列线图的 Harrell 一致性指数均高于 TNM 分期单独使用的指数(0.78 与 0.77,p < 0.001)。我们的列线图成功预测了 CRC 患者的 OS。HRG 的 mRNA 表达水平可能是预测 CRC 结局的辅助标志物。