Abstract
Immune microenvironment of prostate cancer (PCa) is implicated in disease progression. However, previous studies have not fully explored PCa immune microenvironment. This study used ssGSEA algorithm to explore expression levels of 53 immune terms in a combined PCa cohort (eight cohorts; 1,597 samples). The top 10 immune terms were selected based on the random forest analysis and used for immune-related risk score (IRS) calculation. Furthermore, we explored differences in clinical and genomic features between high and low IRS groups. An IRS signature based on the 10 immune terms showed high prediction potential for PCa prognosis. Patients in the high IRS group showed significantly higher percentage of immunotherapy response factors, implying that IRS is effective in predicting immunotherapy response rate. Furthermore, consensus clustering was performed to separate the population into three IRSclusters with different clinical outcomes. Patients in IRScluster3 showed the worst prognosis and highest immunotherapy response rate. On the other hand, patients in IRScluster2 showed better prognosis and low immunotherapy response rate. In addition, VGLL3, ANPEP, CD38, CCK, DPYS, CST2, COMP, CRISP3, NKAIN1, and F5 genes were differentially expressed in the three IRSclusters. Furthermore, CMap analysis showed that five compounds targeted IRS signature, thioridazine, trifluoperazine, 0175029-0000, trichostatin A, and fluphenazine. In summary, immune characteristics of PCa tumor microenvironment was explored and an IRS signature was constructed based on 10 immune terms. Analysis showed that this signature is a useful tool for prognosis and prediction of immunotherapy response rate of PCa.
Highlights
Prostate cancer (PCa) is the most common urological malignant tumor in men and the second leading cause of cancer-related death in men in the Western world [1]
We developed a new scoring tool named immune-related risk score (IRS) based on 53 immune terms quantified by single-sample gene set enrichment analysis (ssGSEA)
Our study evaluated the immune environment of prostate cancer (PCa) patients based on a combined cohort of a large population
Summary
Prostate cancer (PCa) is the most common urological malignant tumor in men and the second leading cause of cancer-related death in men in the Western world [1]. Radical prostatectomy is the conventional treatment approach for localized PCa. 25%–30% PCa patients who undergo radical prostatectomy progress to advanced disease stage associated with high recurrence and poor prognosis within 10 years [2]. Most metastatic PCa do not Immune Landscape in Prostate Cancer undergo full remission and are associated with severe symptoms as a result of osseous metastases, despite long-term survival [3]. Androgen deprivation therapy (ADT), such as enzalutamide and abiraterone, is the conventional approach for treatment of advanced and metastasized PCa. most patients initially show high response rate to hormone therapy, they invariably evolve to castrate-resistant prostate cancer (CRPC) after several years. CRPC patients undergo chemoradiotherapy such as cyclophosphamide and methotrexate, yet the approach is associated with limited efficacy and severe side effects [5]. The limitations for current therapy approaches call for the need to explore potential mechanism of PCa progression and novel targets to improve therapeutic intervention
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