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An Immunophenotyping of Ovarian Cancer With Clinical and Immunological Significance.

ABSTRACT: Immune checkpoint blockade (ICB), mainly anti-CTLA-4 and anti-PD-1/PD-L1 therapy, has showed promising clinical benefits in the treatment of some cancer types; however, its application in ovarian cancer is still in the primary stage. Immunophenotyping can help us understand the clinical characteristics and immune status of cancer, and thus benefit immunotherapy and personalized therapy. In this study, we clustered 907 ovarian cancer patients into three immune molecular subtypes (IMMSs) based on 48 genes. Expression data were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering was used to identify IMMS. Clinical and immunological characteristics and gene expression patterns of different IMMS were compared, and associations between IMMS and tumor microenvironment immune types were explored. Three IMMSs with different clinical and immunological characteristics were identified, in which type I and II ovarian cancer patients were similar to each other. There were more serous and low-grade tumors in type I and II ovarian cancer. IMMS was associated with disease-free survival before and after adjusting for clinical characteristics and ICB-related genes. Among the differentially expressed genes identified in our study, about 90% (25/28) were highly expressed in type I and II ovarian cancer. Genes related to ICB (CTLA-4, PD-L1, and PD-L2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type I and II ovarian cancer. Patients with type I and II ovarian cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies. In contrast, patients with type III ovarian cancer may be insensitive to these treatments and require new therapies.

SUBMITTER: Yang K

PROVIDER: S-EPMC7394551 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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An Immunophenotyping of Ovarian Cancer With Clinical and Immunological Significance.

Yang Kai K Zhao Weiwei W Lou Ge G Rong Zhiwei Z Xu Huan H Wang Wenjie W Song Wei W Cai Yuqing Y Hou Yan Y Li Kang K

Frontiers in immunology 20180410

Immune checkpoint blockade (ICB), mainly anti-CTLA-4 and anti-PD-1/PD-L1 therapy, has showed promising clinical benefits in the treatment of some cancer types; however, its application in ovarian cancer is still in the primary stage. Immunophenotyping can help us understand the clinical characteristics and immune status of cancer, and thus benefit immunotherapy and personalized therapy. In this study, we clustered 907 ovarian cancer patients into three immune molecular subtypes (IMMSs) based on ...[more]

PMID: 32793247

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Project description:ObjectiveEpithelial ovarian cancer (EOC) is a heterogeneous disease with diverse clinicopathological features and behaviors, and its heterogeneity may be concerned with the accumulation of multiple somatic oncogenic mutations. The major goals of this study are to systematically perform the comprehensive mutational profiling in EOC patients, and investigate the associations between somatic mutations and clinicopathological characteristics.MethodsA total of 80 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery, and genomic DNAs were extracted from fresh-frozen tissues. We investigated mutational status in hot spot regions of 50 cancer-related genes by targeted next-generation sequencing using an Ion AmpliSeq Cancer Hotspot Panel v2 Kit.ResultsValidated mutations were detected in 66 of the 80 tumors (82.5%). The five most frequently mutated genes were TP53 (43.8%), PIK3CA (27.5%), KRAS (23.8%), PTEN (10%) and CTNNB1 (10%). PTEN and CTNNB1 mutations were associated with younger age. PIK3CA1, KRAS and CTNNB1 mutations were observed in early-stage, whereas TP53 mutations were more common in advanced stage. Significant associations were observed between TP53 mutation and serous carcinoma, and between KRAS mutation and mucinous carcinoma. Both PIK3CA mutation and CTNNB1 mutation were also significantly associated with endometrioid and clear cell carcinoma. The patients with PIK3CA and KRAS mutations were significantly associated with favorable progression free survival (PFS). In particular, PIK3CA mutations had more significant associations with favorable PFS than PIK3CA wild-type in the endometrioid subtype (P = 0.012). Patients with mutations only in TP53 were significantly associated with worse PFS.ConclusionEOCs were heterogeneous at the genomic level and harbored somatic oncogenic mutations. Our molecular profiling may have the potential for becoming a novel stratification within histological subtypes of EOC. Further studies are needed to define molecular classification for improved clinical outcomes and treatment of EOC patients in future.

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An Immunophenotyping of Ovarian Cancer With Clinical and Immunological Significance.

Publications

An Immunophenotyping of Ovarian Cancer With Clinical and Immunological Significance.

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