Integrative genomic and transcriptomic analysis reveals immune subtypes and prognostic markers in ovarian clear cell carcinoma

BACKGROUND: We performed an integrative genomic and transcriptomic profiling to identify molecular subtypes and prognostic markers with special focus on immune-related pathways. METHODS: Totally, 50 Chinese patients were subjected to targeted next-generation sequencing and transcriptomic sequencing. RESULTS: Two distinct subgroups were identified as immune (22.0%) and non-immune (78.0%) based on the immune-pathway related hierarchical clustering. Surprisingly, patients with immune subtype had a significantly worse survival. The prognostic capacity was validated in external cohorts. The immune group had higher expression of genes involved in pro-inflammation and checkpoints. PD-1 signalling pathway was enriched in the immune subtype. Besides, the immune cluster presented enriched expression of genes involved in epithelial-mesenchymal transition, angiogenesis and PI3K-AKT-mTOR signalling, while the non-immune subtype had higher expression of metabolic pathways. The immune subtype had a higher mutation rate of PIK3CA though significance was not achieved. Lastly, we established a prognostic immune signature for overall survival. Interestingly, the immune signature could also be applied to renal clear cell carcinoma, but not to other histologic subtype of ovarian cancer. CONCLUSIONS: An immune subtype of OCCC was identified with poor survival and enrichment of PD-1 and PI3K-AKT-mTOR signalling. We constructed and validated a robust prognostic immune signature of OCCC patients.