Bu Luping, Huang Fengxing, Li Mengting, Peng Yanan, Wang Haizhou, Zhang Meng, Peng Liqun, Liu Lan, Zhao Qiu
Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China.
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.
PeerJ. 2021 May 13;9:e11430. doi: 10.7717/peerj.11430. eCollection 2021.
Colorectal cancer (CRC) is one of the most common malignant carcinomas worldwide with poor prognosis, imposing an increasingly heavy burden on patients. Previous experiments and epidemiological studies have shown that vitamin D and vitamin D-related genes play a vital role in CRC. Therefore, we aimed to construct a vitamin D-related gene signature to predict prognosis in CRC. The CRC data from The Cancer Genome Atlas (TCGA) was performed as the training set. A total of 173 vitamin D-related genes in the TCGA CRC dataset were screened, and 17 genes associated with CRC prognosis were identified from them. Then, a vitamin D-related gene signature consisting of those 17 genes was established by univariate and multivariate Cox analyses. Moreover, four external datasets (GSE17536, GSE103479, GSE39582, and GSE17537) were used as testing set to validate the stability of this signature. The high-risk group presented a significantly poorer overall survival than low-risk group in both of training set and testing sets. Besides, the areas under the curve (AUCs) for signature on OS in training set at 1, 3, and 5 years were 0.710, 0.708, 0.710 respectively. The AUCs of the ROC curve in GSE17536 for 1, 3, and 5 years were 0.649, 0.654, and 0.694. These results indicated the vitamin D-related gene signature model could effectively predict the survival status of CRC patients. This vitamin D-related gene signature was also correlated with TNM stage in CRC clinical parameters, and the higher risk score from this model was companied with higher clinical stage. Furthermore, the high accuracy of this prognostic signature was validated and confirmed by nomogram model. In conclusion, we have proposed a novel vitamin D-related gene model to predict the prognosis of CRC, which will help provide new therapeutic targets and act as potential prognostic biomarkers for CRC.
结直肠癌(CRC)是全球最常见的恶性肿瘤之一,预后较差,给患者带来日益沉重的负担。先前的实验和流行病学研究表明,维生素D及与维生素D相关的基因在结直肠癌中起着至关重要的作用。因此,我们旨在构建一个与维生素D相关的基因特征来预测结直肠癌的预后。来自癌症基因组图谱(TCGA)的结直肠癌数据用作训练集。在TCGA结直肠癌数据集中筛选出总共173个与维生素D相关的基因,并从中鉴定出17个与结直肠癌预后相关的基因。然后,通过单变量和多变量Cox分析建立了由这17个基因组成的与维生素D相关的基因特征。此外,使用四个外部数据集(GSE17536、GSE103479、GSE39582和GSE17537)作为测试集来验证该特征的稳定性。在训练集和测试集中,高风险组的总生存期均显著低于低风险组。此外,训练集中1年、3年和5年时该特征对总生存期的曲线下面积(AUC)分别为0.710、0.708、0.710。GSE17536中1年、3年和5年时ROC曲线的AUC分别为0.649、0.654和0.694。这些结果表明,与维生素D相关的基因特征模型可以有效地预测结直肠癌患者的生存状况。该与维生素D相关的基因特征还与结直肠癌临床参数中的TNM分期相关,并且该模型的风险评分越高,临床分期越高。此外,列线图模型验证并证实了该预后特征的高准确性。总之,我们提出了一种新的与维生素D相关的基因模型来预测结直肠癌的预后这将有助于提供新的治疗靶点,并作为结直肠癌潜在的预后生物标志物。