A comprehensive analysis of IDO1 expression with tumour-infiltrating immune cells and mutation burden in gynaecologic and breast cancers

对妇科肿瘤和乳腺癌中肿瘤浸润免疫细胞内IDO1表达及突变负荷进行全面分析

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Abstract

Gynaecologic and breast cancers share some similarities at the molecular level. The aims of our study are to highlight the similarities and differences about IDO1, an important immune-related gene in female cancers. The NGS data from TCGA of cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and breast invasive carcinoma (BRCA) were analysed to identify molecular features, and clinically significant and potential therapeutic targets of IDO1. We found IDO1 was significantly up-regulated in four gynaecologic cancers and breast cancer. According to breast cancer PAM50 classification scheme, IDO1 expression was higher in tumours of basal than other subtypes and showed better survival prognosis in BRCA and OV. Through immune infiltration analysis, we found a strong correlation between IDO1 and immune cell populations especially for dendritic cells and T cells. In addition, we investigated the association between IDO1 and tumour mutation burden (TMB) and found that IDO1 was significantly correlated with TMB in BRCA and CESC. GSVA revealed that hallmarks significantly correlated with IDO1 were involved in interferon gamma response, allograft rejection and inflammatory response. We also found PD-L1 and LAG3 were highly positive related to IDO1 in gynaecologic cancers when comparing with their corresponding normal tissues. Our results indicated that IDO1 participated in anti-tumour immune process and is correlated with mutation burden. These findings may expand our outlook of potential anti-IDO1 treatments.

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