Journal
FRONTIERS IN ONCOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.01532
Keywords
prostate cancer; prognostic biomarker; tumor immune microenvironment; copy number variations; molecule drugs
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Funding
- Medical Science and Technology Innovation Platform support project of Zhongnan Hospital of Wuhan University [PTXM2019006]
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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.
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