Establishment of a Novel Combined Nomogram for Predicting the Risk of Progression Related to Castration Resistance in Patients With Prostate Cancer

作者全名："Li, Shuqiang; Shi, Lei; Li, Fan; Yao, Bing; Chang, Liansheng; Lu, Hongyan; Song, Dongkui"

作者地址："[Li, Shuqiang; Shi, Lei; Li, Fan; Yao, Bing; Chang, Liansheng; Song, Dongkui] Zhengzhou Univ, Affiliated Hosp 1, Dept Urol, Zhengzhou, Peoples R China; [Lu, Hongyan] Chongqing Med Univ, Affiliated Hosp 3, Dept Urol, Chongqing, Peoples R China"

通信作者："Li, SQ; Song, DK (通讯作者)，Zhengzhou Univ, Affiliated Hosp 1, Dept Urol, Zhengzhou, Peoples R China."

来源：FRONTIERS IN GENETICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000802266400001

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：prostate cancer; castration resistance; progression; nomogram; KIFC2; BCAS1

摘要："Background: The emergence of castration resistance is fatal for patients with prostate cancer (PCa); however, there is still a lack of effective means to detect the early progression. In this study, a novel combined nomogram was established to predict the risk of progression related to castration resistance.Methods: The castration-resistant prostate cancer (CRPC)-related differentially expressed genes (DEGs) were identified by R packages ""limma"" and ""WGCNA"" in GSE35988-GPL6480 and GSE70768-GPL10558, respectively. Relationships between DEGs and progression-free interval (PFI) were analyzed using the Kaplan-Meier method in TCGA PCa patients. A multigene signature was built by lasso-penalized Cox regression analysis, and assessed by the receiver operator characteristic (ROC) curve and Kaplan-Meier curve. Finally, the univariate and multivariate Cox regression analyses were used to establish a combined nomogram. The prognostic value of the nomogram was validated by concordance index (C-index), calibration plots, ROC curve, and decision curve analysis (DCA).Results: 15 CRPC-related DEGs were identified finally, of which 13 genes were significantly associated with PFI and used as the candidate genes for modeling. A two-gene (KIFC2 and BCAS1) signature was built to predict the risk of progression. The ROC curve indicated that 5-year area under curve (AUC) in the training, testing, and whole TCGA dataset was 0.722, 0.739, and 0.731, respectively. Patients with high-risk scores were significantly associated with poorer PFI (p < 0.0001). A novel combined nomogram was successfully established for individualized prediction integrating with T stage, Gleason score, and risk score. While the 1-year, 3-year, and 5-year AUC were 0.76, 0.761, and 0.762, respectively, the good prognostic value of the nomogram was also validated by the C-index (0.734), calibration plots, and DCA.Conclusion: The combined nomogram can be used to predict the individualized risk of progression related to castration resistance for PCa patients and has been preliminarily verified to have good predictive ability."

基金机构：key scientific and technological projects of Henan Province [192102310120]; Postdoctoral Natural Science Foundation of Chongqing [cstc2020jcyj-bshX0028]

基金资助正文：Funding This work was supported by the key scientific and technological projects of Henan Province (Project No. 192102310120) and Postdoctoral Natural Science Foundation of Chongqing (cstc2020jcyj-bshX0028).