Abstract
Objectives: Prostate cancer (PC) is the second most frequent tumor in men, which has a high recurrence rate and poor prognosis. Therefore, this study aimed to identify novel prognostic biomarkers and therapeutic targets for immunotherapy and small molecule drugs for PC treatment.Materials and Methods: The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to calculate immune scores and stromal scores of TCGA-PRAD data. Differentially expressed genes (DEGs) were identified using R package “limma.” GO, KEGG, and DO analyses were performed to analyze DEGs. Overall survival and disease-free survival analyses were conducted for hub gene identification. To validate the hub gene at the mRNA and protein expression levels, genetic alterations were measured, and CCLE and Cox regression analyses were performed. Connectivity map (CMap) analysis and GSEA were performed for drug exploration and function analysis, respectively.Results: Immune scores ranged from −1795.98 to 2339.39, and stomal scores ranged from −1877.60 to 1659.96. In total, 45 tumor microenvironment (TME)-related DEGs were identified, of which Complement C7 (C7) was selected and validated as a hub gene. CMap analysis identified six small molecule drugs as potential agents for PC treatment. Further analysis demonstrated that C7 expression was significantly correlated with clinical T, pathological N, and immune infiltration level.Conclusions: In conclusion, of the 45 TME-related DEGs, C7 was shown to correlate with PC prognosis in patients, indicating it as a novel prognostic biomarker and immunotherapy target in PC. Additionally, six small molecule drugs showed strong therapeutic potential for PC treatment.
Highlights
Prostate cancer (PC) is the second most frequent tumor in men, with a high recurrence rate and age dependence [1]
Among the 495 PCs downloaded from the The Cancer Genome Atlas (TCGA) database, 69.5% (n = 344) samples were pathological N0, and 15.8% (n = 78) samples were pathological N1
Clinical M0 accounted for 91.5% (n = 453), while clinical M1 accounted for 0.6% (n = 3)
Summary
Prostate cancer (PC) is the second most frequent tumor in men, with a high recurrence rate and age dependence [1]. Serum PSA, CT, and magnetic resonance examination have been widely used for PC diagnosis, these methods do not show high accuracy and specificity [2]. Novel biomarkers to accurately diagnose PC are needed. More studies have shown that immunotherapy could treat cancers effectively and safely [3,4,5]. With the development of immunotherapy for cancers, more and more researchers focus on finding out more accurate therapeutic targets for immune treatment [6, 7]. In this study, we aimed to screen some novel diagnostic and prognostic biomarkers for PC and therapeutic targets for immunotherapy
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