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Integrative analysis of genomic and epigenetic regulation of endometrial cancer

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单位: [1]Peking Univ, Ctr Reprod Med, Dept Obstet & Gynecol, Hosp 3, Beijing 100191, Peoples R China [2]Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing 100191, Peoples R China [3]Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China [4]Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Syst Biomed, Beijing 100191, Peoples R China [5]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430000, Peoples R China [6]Guangzhou Med Univ, Key Lab Major Obstetr Dis Guangdong Prov, Affiliated Hosp 3, Guangzhou 510150, Peoples R China [7]Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
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关键词: proliferation apoptosis glycolysis Wnt/beta-catenin gemcitabine

摘要:
Endometrial carcinomas (EC) are characterized by high DNA copy numbers and DNA methylation aberrations. In this study, we sought to comprehensively explore the effect of these two factors on development and progression of EC by analyzing integrated genomic and epigenetic analysis to. We found high DNA copy number and DNA methylation abnormalities in EC, with 6308 copy-number variation genes (CNV-G) and 4376 methylation genes (MET-G). We used these CNV-G and MET-G to subcategorize the samples for prognostic analysis, and identified three molecular subtypes (iC1, iC2, iC3). Moreover, the subtypes exhibited different tumor immune microenvironment characteristics. A further analysis of their molecular characteristics revealed three potential prognostic markers (KIAA1324, nonexpresser of pathogenesis-related genes1 (NPR1) and idiopathic hypogonadotropic hypogonadism (IHH)). Notably, all three markers showed distinct CNV, DNA methylation, and gene expression profiles. Analysis of mutations among the three subtypes revealed that iC2 had fewer mutations than the other subtypes. Conversely, iC2 showed significantly higher CNV levels than other subtypes. This comprehensive analysis of genomic and epigenetic profiles identified three prognostic markers, therefore, provides new insights into the multi-layered pathology of EC. These can be utilized for accurate treatment of EC patients.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 老年医学 3 区 细胞生物学
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出版当年[2018]版:
Q1 GERIATRICS & GERONTOLOGY Q1 CELL BIOLOGY
最新[2023]版:
Q2 CELL BIOLOGY Q2 GERIATRICS & GERONTOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者单位: [1]Peking Univ, Ctr Reprod Med, Dept Obstet & Gynecol, Hosp 3, Beijing 100191, Peoples R China [4]Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Syst Biomed, Beijing 100191, Peoples R China
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通讯机构: [1]Peking Univ, Ctr Reprod Med, Dept Obstet & Gynecol, Hosp 3, Beijing 100191, Peoples R China [2]Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing 100191, Peoples R China [3]Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China
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