Lin Han, Wang Jiamin, Wen Xiaohui, Wen Qidan, Huang Shiya, Mai Zhefen, Lu Lingjing, Liang Xingyan, Pan Haixia, Li Shuna, He Yuhong, Ma Hongxia
Department of Gynecology of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China.
Department of Urology and Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China.
Oncol Lett. 2020 Nov;20(5):204. doi: 10.3892/ol.2020.12067. Epub 2020 Sep 8.
Ovarian carcinoma (OV) is one of the most lethal gynecological malignancies globally, and the overall 5-year survival rate of OV was 47% in 2018 according to American data. To increase the survival rate of patients with OV, many researchers have sought to identify biomarkers that act as both prognosis-predictive markers and therapy targets. However, most of these have not been suitable for clinical application. The present study aimed at constructing a predictive prognostic nomogram of OV using the genes identified by combining The Cancer Genome Atlas (TCGA) dataset for OV with the immune score calculated by the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm. Firstly, the algorithm was used to calculate the immune score of patients with OV in the TCGA-OV dataset. Secondly, differentially expressed genes (DEGs) between low and high immune score tissues were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed to predict the functions of these DEGs. Thirdly, univariate, multivariate and Lasso Cox's regression analyses were carried out step by step, and six prognosis-related DEGs were identified. Then, Kaplan-Myer survival curves were generated for these genes and validated by comparing their expression levels to further narrow the range of DEGs and to calculate the risk score. Two genes were identified, cell division cycle 20B and patatin-like phospholipase domain containing 5, which were both shown to have higher expression levels in OV tissues and to be significantly associated with the prognosis of OV. Next, a nomogram was created using these two genes and age, and using the receiver operating characteristic (ROC) curve and calibration curve, the effectiveness of the nomogram was validated. Finally, an external validation was conducted for this nomogram. The ROC showed that the areas under the curve (AUCs) of the 3- and 5-year overall survival predictions for the nomogram were 0.678 and 0.62, respectively. Moreover, the ROC of the external validation model showed that the AUCs of the 3- and 5-year were 0.699 and 0.643, respectively, demonstrating the effectiveness of the generated nomogram. In conclusion, the present study has identified two immune-related genes as biomarkers that reliably predict overall survival in OV. These biomarkers might also be potential molecular targets of immune therapy to treat patients with OV.
卵巢癌(OV)是全球最致命的妇科恶性肿瘤之一,根据美国数据,2018年OV的总体5年生存率为47%。为提高OV患者的生存率,许多研究人员试图识别既作为预后预测标志物又作为治疗靶点的生物标志物。然而,其中大多数并不适合临床应用。本研究旨在利用通过将OV的癌症基因组图谱(TCGA)数据集与使用表达数据算法在恶性肿瘤组织中估计基质和免疫细胞(ESTIMATE)计算的免疫评分相结合而鉴定的基因,构建OV的预测性预后列线图。首先,使用该算法计算TCGA-OV数据集中OV患者的免疫评分。其次,鉴定低免疫评分组织和高免疫评分组织之间的差异表达基因(DEG),并进行基因本体论和京都基因与基因组百科全书分析以预测这些DEG的功能。第三,逐步进行单变量、多变量和套索Cox回归分析,鉴定出6个与预后相关的DEG。然后,针对这些基因生成Kaplan-Meier生存曲线,并通过比较它们的表达水平进行验证,以进一步缩小DEG范围并计算风险评分。鉴定出两个基因,即细胞分裂周期20B和含patatin样磷脂酶结构域5,它们在OV组织中均显示出较高的表达水平,并且与OV的预后显著相关。接下来,使用这两个基因和年龄创建列线图,并使用受试者工作特征(ROC)曲线和校准曲线验证列线图的有效性。最后,对该列线图进行外部验证。ROC显示,列线图对3年和5年总生存预测的曲线下面积(AUC)分别为0.678和0.62。此外,外部验证模型的ROC显示,3年和5年的AUC分别为0.699和0.643,证明了所生成列线图的有效性。总之,本研究已鉴定出两个与免疫相关的基因作为可靠预测OV总生存的生物标志物。这些生物标志物也可能是治疗OV患者的免疫治疗的潜在分子靶点。