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pmid:33758613
Identification of a Prognostic Signature Model with Tumor Microenvironment for predicting Disease-free Survival after Radical Prostatectomy.
Hao Zhao · Xuening Zhang · Zhan Shi · Bingxin Guo · Wenli Zhang · Kun He · Xueqi Hu · Songhe Shi
Journal of Cancer · 2021 doi:10.7150/jca.51173
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Complete file
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We attempted to identify the important prognostic genes and prognostic characteristics related to TME in prostate cancer (PCa). Methods: The gene transcriptome profiles and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database, and the immune and stromal scores were calculated by the ESTIMATE algorithm. We evaluated the prognostic value of the risk score (RS) model based on univariate Cox analysis and least absolute shrinkage and selection operation (LASSO) Cox regression analysis and established a nomogram to predict disease-free survival (DFS) in PCa patients. The GSE70768 dataset was utilized for external validation. Twenty-two subsets of tumor-infiltrating immune cells were analyzed using the CIBERSORT algorithm. Results: In this study, the patients with higher immune/stromal scores were associated with a worse DFS, higher Gleason score, and higher pathological T stage. Based on the immune and stromal scores, 515 differentially expressed genes (DEGs) were identified. The univariate Cox and LASSO Cox regression models were employed to select 18 DEGs from 515 DEGs and construct an RS model. The DFS of the high-RS group was significantly lower than that of the low-RS group (P<0.001). The AUCs for the 1-year, 3-year and 5-year DFS rates in the RS model were 0.890, 0.877 and 0.841, respectively. A nomogram of DFS was established based on the RS and Gleason score, and the AUCs for the 1-year, 3-year and 5-year DFS rates in the nomogram were 0.907, 0.893, and 0.872, respectively. These results were further validated in the GSE70768 dataset. In addition, the proportion of Tregs was determined to be higher in high-RS patients (P<0.05), and the expression levels of five immune checkpoints (CTLA-4, PD-1, LAG-3, TIM-3 and TIGIT) were observed to be higher in high-RS patients (P<0.05). 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