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鉴定与 BRCA1 突变、免疫检查点和卵巢癌临床结局相关的免疫增强分子亚型。

Identification of immune-enhanced molecular subtype associated with BRCA1 mutations, immune checkpoints and clinical outcome in ovarian carcinoma.

机构信息

Department of Gynaecology and Obstetrics, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.

Key Laboratory Of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China.

出版信息

J Cell Mol Med. 2020 Mar;24(5):2819-2831. doi: 10.1111/jcmm.14830. Epub 2020 Jan 29.

Abstract

Ovarian carcinoma has the highest mortality among the malignant tumours in gynaecology, and new treatment strategies are urgently needed to improve the clinical status of ovarian carcinoma patients. The Cancer Genome Atlas (TCGA) cohort were performed to explore the immune function of the internal environment of tumours and its clinical correlation with ovarian carcinoma. Finally, four molecular subtypes were obtained based on the global immune-related genes. The correlation analysis and clinical characteristics showed that four subtypes were all significantly related to clinical stage; the immune scoring results indicated that most immune signatures were upregulated in C3 subtype, and the majority of tumour-infiltrating immune cells were upregulated in both C3 and C4 subtypes. Compared with other subtypes, C3 subtype had a higher BRCA1 mutation, higher expression of immune checkpoints, and optimal survival prognosis. These findings of the immunological microenvironment in tumours may provide new ideas for developing immunotherapeutic strategies for ovarian carcinoma.

摘要

卵巢癌是妇科恶性肿瘤中死亡率最高的肿瘤,迫切需要新的治疗策略来改善卵巢癌患者的临床状况。对癌症基因组图谱(TCGA)队列进行分析,以探讨肿瘤内部环境的免疫功能及其与卵巢癌的临床相关性。最后,基于全局免疫相关基因得到了四个分子亚型。相关性分析和临床特征表明,四个亚型均与临床分期显著相关;免疫评分结果表明,C3 亚型中大多数免疫特征上调,C3 和 C4 亚型中大多数肿瘤浸润免疫细胞上调。与其他亚型相比,C3 亚型具有更高的 BRCA1 突变率、更高的免疫检查点表达和最佳的生存预后。这些肿瘤免疫微环境的发现可能为开发卵巢癌的免疫治疗策略提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d615/7077593/ddc4ff232436/JCMM-24-2819-g001.jpg

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