Immune and Stromal Score-Related Gene Signatures For Risk Stratification of Gynaecologic Cancers

Abstract

Background: The immune and stromal landscape of gynaecologic cancers is far from elucidated, and there is a lack of systematic prognostic analysis of the immune or stromal parts of the tumour microenvironment (TME) in all types of gynaecologic cancers. We aimed to establish immune and stromal score-based risk signatures for each type of gynaecologic cancer.Methods: In the present study, using the algorithm of “Estimation of stromal and immune cells in malignant tumours using expression data”, we calculated immune and stromal scores for cervical squamous carcinoma (CESC), uteri corpus endometrial cancer (UCEC) and ovarian cancer (OVCA) from the cancer genome atlas (TCGA) to establish immune and stromal score-based risk signatures. Multi-omics analysis combining single nucleotide polymorphism (SNP), tumour mutation burden (TMB) and gene set variation analysis was further performed to investigate the mechanism of immune and stromal score-based risk signatures in gynaecologic cancers. Eventually, the prognostic value of some signature genes was examined in independent microarrays and aberrant expression of IHH in UCECs through immunohistochemistry. Results: According to the results, the prognosis prediction ability of the immune and stromal score-related risk signatures constructed for pan-gynaecological cancers withstood the tests of tROC curves and Kaplan-Meier survival curves, proving to be effective in risk stratification. Three signature genes, including BNC1, CCDC80, and IHH, were verified in independent datasets to have prognostic value in gynaecologic cancers. Conclusions: In summary, the immune and stromal score-related risk signature constructed in this study might be promising prognostic markers for pan-gynaecological cancers.