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Prostate cancer
By Lu DJ, Liang HQ, Li YJ and 9 others.
Previous studies have found that PROK1 is involved in the progression of tumors. This study aims to investigate the association of PROK1 with prognosis and its potential relationship with the efficacy of antiandrogen therapy in prostate cancer and to explore the underlying mechanisms.
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A total of 498 and 1249 prostate cancer samples were obtained from the TCGA and GEO databases, respectively. First, the expression of PROK1 in prostate cancer was analyzed in the bulk RNA sequencing dataset, and the prognostic value of PROK1 was explored. Subsequently, pseudotime analysis and virtual knockout were conducted in the single-cell RNA sequencing dataset to investigate its biological function in tumor progression. Further cell communication analysis revealed the interactions between cells. Additionally, the predictive function and changes of PROK1 expression in antiandrogen therapy were explored through the GDSC database and in vitro experiments.
PROK1 was downregulated in prostate cancer and decreased with advancing TNM stage. Meta-analysis also showed lower PROK1 expression in tumor and metastatic prostate cancer compared to controls. Single-cell RNA sequencing analysis suggested that PROK1 was specifically highly expressed in mesenchymal stem cells (MSC)-like stromal cells. Virtual knockout of the PROK1 perturbation analysis revealed that the differentially expressed genes were enriched in insulin-like growth factor receptor signaling pathway. Moreover, PROK1-positive stromal cells had stronger IGFBP signal communication with prostate cancer cells. Additionally, PROK1 and IGFBP7 showed spatial expression colocalization. High PROK1 expression in prostate cancer was associated with higher sensitivity to bicalutamide. However, PROK1 expression decreases after antiandrogen therapy.
Low PROK1 expression is associated with worse prognosis and may correlate with reduced antiandrogen therapy efficacy. Downregulation of PROK1 after antiandrogen therapy may be related to the treatment resistance.
Published in Prostate cancer. The abstract is shown as published and remains the work of its authors; read the full article at the source.
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