A novel hypoxia-related genes signature for prognosis and immunotherapeutic sensitivity in uterine carcinosarcoma patients

Uterine carcinosarcoma (UCS) is a kind of rare malignancy hard to diagnose and cure. Hypoxia-related genes (HRGs) are proved to be related with tumor prognosis and its microenvironment. Still, the prognostic potential of HRGs in UCS patients remains to be clarified. HRGs were comprehensively analyzed and TCGA database was used to extract DEGs. A prognostic model was constructed to determine the association between HRGs and the prognosis of UCS patients from TCGA cohort. Validation was done in ICGC cohort. The relationship between functional enrichment of these genes and the sensitivity of immunotherapy in UCS was investigated. TIDE value and immunotherapy sensitivity were also estimated in current research. ANGPT2, PLOD1, HSF1, KCNMA1, 36L1 and CCNB1 hypoxia-related signatures were finally selected to estimate prognosis. The results in the analysis of TCGA and GEO database both showed that high -risk group has a poorer survival. Functions of hypoxia-related genes are related with signaling pathways and immune response. Sorts of immune cells always expressed higher stage in low-risk group. Gene marker PD-L1, PDL2, CD80 also have various expression in different groups with strongly statistical significance. Moreover, low-risk group showed a higher sensitivity to immunotherapy. A prognostic model of UCS based on hypoxia gene was performed with high ac-curacy. There are significant differences in the immune status of patients in high-risk group and low-risk group, based on hypoxia-related genes signature. Moreover, patients in high-risk group and low-risk group have different sensitivity to immunotherapy, which can provide a reference for clinical treatment.