An Integrative Omics Approach to Identify Biomarkers Related to Preeclampsia and Breast Cancer Risks

识别与先兆子痫和乳腺癌风险相关的生物标志物的综合组学方法

• 批准号: 9162127
• 负责人: Lana X Garmire
• 金额: $ 63.66万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-19 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9162127
• 关键词: AFP gene; Accounting; Adult; Big Data; Bioinformatics; Biological; Biological Markers; Birth; Blood; Blood specimen; Child; Chronic Disease; Classification; Computing Methodologies; DNA; DNA Methylation; Data; Data Analyses; Disease; Environment; Epidemiologic Studies; Epigenetic Process; Ethics; Etiology; Female; Genes; Genomics; Goals; Hawaii; Hormones; Human; Hypertension; Intervention; Level of Evidence; Life; Link; Malignant Neoplasms; Mediator of activation protein; Medical; Modeling; Molecular; Morbidity - disease rate; Mothers; Nested Case-Control Study; Pathway interactions; Physical Exercise; Pilot Projects; Placenta; Play; Population; Pre-Eclampsia; Predisposition; Pregnancy; Pregnant Women; Prevention; Progesterone; Proteinuria; Proteome; Proteomics; Research Personnel; Role; Sampling; Tamoxifen; Testing; The Cancer Genome Atlas; Tissues; Umbilical Cord Blood; Universities; Woman; biobank; cancer prevention; cancer risk; case control; cohort; data integration; epigenetic regulation; epigenome; epigenomics; follow-up; genetic signature; genome-wide; improved; in utero; malignant breast neoplasm; medical schools; methylome; mortality; novel; offspring; peripheral blood; pregnant; protective effect; repository; research study; secretory protein; targeted treatment; theories; therapeutic biomarker; therapeutic target; tool; transcriptome; transcriptome sequencing; unborn child

PROJECT SUMMARY Preeclampsia is the medical condition characterized by hypertension and proteinuria in pregnant women. It occurs in 5 to 8% of all pregnancies (as common as breast cancer) and is the leading cause of morbidity and mortality for both the mother and the unborn child. Surprisingly, epidemiological studies have shown strong evidence that women associated with preeclamptic pregnancies have almost 50% reduced rate of breast cancers decades later. However, due to ethical and practical reasons, direct evidence from long-term follow up in human population is lacking. Moreover, the underlying mechanism to explain the lasting effect of preeclampsia remains unknown. Here we propose an alternative and integrative omics approach to investigate the molecular links between preeclampsia and breast cancer risks later in life. We will conduct a nested case control study to investigate the epigenome, RNA-Seq transcriptome and proteomics differences in the placenta and matched maternal blood DNA samples associated with preeclampsia. The de-identified samples will be collected through the Hawaii Biorepository (HiBR), and they reflect the unique multi-ethnic population of Hawaii. We will construct bioinformatics pipelines to analyze all three types of omics data individually, and develop new computational methods for omics data integration. We will identify coherent genes, modules and biological pathways as the biomarkers of preeclampsia. Moreover, we will compare our data with the DNA methylome, RNA-Seq transcriptome, and proteomics data of the breast cancer samples from The Cancer Genome Atlas. Through such comparison, we will uncover the cancer-related genes, modules and biological pathways within the preeclampsia samples. This will provide direct molecular-level evidence to link preeclampsia and breast cancer risks later in life, which is practically impossible using the approach of population follow-up. It will also identify biomarkers of breast cancer susceptibility as early as a child's birth, for the purpose of cancer prevention.

项目总结