Department of Urology, Affiliated Hospital of Nantong University, No.20 West Temple Road, Nantong, Jiangsu Province, 226001, China.
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China.
BMC Cancer. 2021 Apr 9;21(1):381. doi: 10.1186/s12885-021-08111-0.
The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration.
Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature.
Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature.
A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients' survival.
糖酵解在肿瘤发生中的作用受到越来越多的关注,并且已经证明多种糖酵解相关基因(GRG)与肿瘤转移有关。因此,我们旨在构建一个基于 GRG 的用于透明细胞肾细胞癌(ccRCC)的预后标志物,并探讨其与免疫浸润的关系。
从癌症基因组图谱(TCGA)和 ArrayExpress 数据集获得 ccRCC 的临床信息和 RNA 测序数据。通过单变量 COX、LASSO 和多变量 COX 回归分析最终选择关键的 GRG。进一步进行外部和内部验证以验证我们建立的标志物。
最终选择了 10 个 GRG 包括 ANKZF1、CD44、CHST6、HS6ST2、IDUA、KIF20A、NDST3、PLOD2、VCAN、FBP1,用于建立一个新的标志物。与低危组相比,高危组的 ccRCC 患者的总生存率(OS)较低(P=5.548E-13),并且我们建立的标志物的 AUC 均高于 0.70。单变量/多变量 Cox 回归分析进一步证明该标志物可作为独立的预后因素(均 P<0.05)。此外,还为 TCGA 和 ArrayExpress 队列中的 ccRCC 创建了预测预后的列线图,以发现建立的标志物与临床因素和 OS 之间的关系。外部和内部验证后所有结果仍然一致。此外,基于我们建立的标志物,有 9 种 21 种肿瘤浸润免疫细胞(TIICs)与高危和低危 ccRCC 患者高度相关。
成功建立并验证了一个基于 10 个预后 GRG 的新标志物,用于预测 ccRCC 的 OS,有助于临床医生更好、更直观地预测患者的生存情况。