Immunogenomic Profiling and Classification of Prostate Cancer Based on HIF-1 Signaling Pathway

Abstract

The HIF-1 signaling pathway plays an important role in the pathogenesis of cancer. Many studies have explored the progression of prostate cancer (PCa) under hypoxic conditions based on transcriptome data; few have uncovered the immunogenomic profiling and prostate cancer classification based on the HIF-1 signaling pathway. This pathway may help to identify the optimal subset of PCa patients responsive to immunotherapy/chemotherapy. The immunogenomic PCa subsets were classified based on profiling of the HIF-1 signaling pathway, using four publicly available PCa datasets. Three PCa subtypes that named as HIF-1 High (HIF-1_H), HIF-1 Medium (HIF-1_M), and HIF-1 Low (HIF-1_L) were identified. Functional enrichment was analyzed in each subtype. Several cancer-associated and immune-related pathways were hyperactivated in the HIF-1_H subtypes. In contrast, HIF-1_L subtypes were enriched in cell cycle and cell repair. Compared with other subtypes, HIF-1_H subtypes have greater immune cell infiltration, anti-tumor immune activity, and better survival prognosis. The submap and TIDE algorithm were used to predict the clinical response to immune checkpoint blockade, and GDSC was employed to screen potential chemotherapeutic targets for the treatment of PCa. Several chemotherapy drugs were identified in the GDSC dataset, including ABT 888, Temsirolimus, and EHT 1864. Meanwhile, HIF-1_H was defined as an early PCa marker, which is more likely to respond to immunotherapy. The identification of immunogenomic PCa subtypes based on the HIF-1 signaling pathway has potential clinical implications for PCa treatment. Immunopositive PCa subtypes will help to explore the reasons for the poor response of PCa to immunotherapy, and it is expected that immunotherapy will guide the personalized treatment of PCa patients.

Keywords: HIF-1 signaling pathway; classification; immunogenomic profiling; prostate cancer; tumor immunity.