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卵巢癌的免疫特征揭示了具有不同预后、免疫风险和分子机制的新细胞亚型。

Immune Characterization of Ovarian Cancer Reveals New Cell Subtypes With Different Prognoses, Immune Risks, and Molecular Mechanisms.

作者信息

Cong Shanshan, Guo Qiuyan, Cheng Yan, He Yanan, Zhao Xibo, Kong Congcong, Ning Shangwei, Zhang Guangmei

机构信息

Department of Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

出版信息

Front Cell Dev Biol. 2020 Dec 21;8:614139. doi: 10.3389/fcell.2020.614139. eCollection 2020.

Abstract

Ovarian cancer (OV) is a considerable threat to the health of women due to its complex mechanisms and atypical symptoms. Various currently available treatments fail to substantially increase the survival rate of OV patients. The tumor microenvironment (TME) is gaining attention due to its role in tumorigenesis and tumor progression. This study mainly investigated the immune characteristics of OV by CIBERSORT and MCP-counter. We reclassified OV into four TME cell subtypes with different prognoses and evaluated the infiltration of the cells in each subtype. The immune risk of diverse subtypes was evaluated based on the immunoscore calculated by Cox regression analysis. The molecular mechanisms and hallmark pathways of the four subtypes were analyzed. The results indicate that the immune procancer cell subtype is associated with the worst prognosis, closely related to the high immune risk group, and characterized by low expression of checkpoints and MHC class I and II molecules, high expression of hypoxia-related genes, high enrichment of the EMT and hypoxia pathways, and low enrichment of the DNA repair and interferon α response pathways. This study contributes to the investigation of immune mechanisms and identifies more effective targets for immunotherapy of OV.

摘要

卵巢癌(OV)因其复杂的机制和非典型症状,对女性健康构成了重大威胁。目前各种可用的治疗方法未能显著提高OV患者的生存率。肿瘤微环境(TME)因其在肿瘤发生和肿瘤进展中的作用而受到关注。本研究主要通过CIBERSORT和MCP-counter研究OV的免疫特征。我们将OV重新分类为四种具有不同预后的TME细胞亚型,并评估了每种亚型中细胞的浸润情况。基于Cox回归分析计算的免疫评分评估了不同亚型的免疫风险。分析了四种亚型的分子机制和标志性通路。结果表明,免疫促癌细胞亚型与最差的预后相关,与高免疫风险组密切相关,其特征是检查点和MHC I类和II类分子表达低,缺氧相关基因表达高,EMT和缺氧通路高度富集,DNA修复和干扰素α反应通路富集低。本研究有助于免疫机制的研究,并为OV免疫治疗确定更有效的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48f2/7779527/c20e78cff4b2/fcell-08-614139-g001.jpg

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