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Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
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Identifying enhancer-driven subtype-specific prognostic markers in breast cancer based on multi-omics data.

Hongying Zhao1, Siwen Zhang1, Xiangzhe Yin1

  • 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Frontiers in Immunology
|October 28, 2022
PubMed
Summary

This study reveals copy number variations (CNVs) in breast cancer enhancers significantly impact gene expression and patient prognosis across subtypes. Identifying specific enhancer-gene and enhancer-lncRNA pairs offers new prognostic biomarkers and therapeutic targets for breast cancer.

Keywords:
breast cancer subtypecopy number variationenhancerlncRNAprognostic marker

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Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Breast cancer is a complex disease with heterogeneous subtypes, impacting patient prognosis and survival.
  • Copy number variations (CNVs) in enhancer regions are key drivers of tumorigenesis by altering target gene expression.

Purpose of the Study:

  • To identify copy number alteration (CNA)-driven enhancers and their target genes in four breast cancer subtypes.
  • To reconstruct subtype-specific regulatory networks involving CNV-driven enhancers, long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs).
  • To evaluate the prognostic value of identified enhancer-gene and enhancer-lncRNA-mRNA pairs as biomarkers.

Main Methods:

  • Integrated analysis of gene expression, copy number, and H3K27ac ChIP-seq data across breast cancer subtypes.
  • Identification of CNA-driven enhancer-gene and enhancer-lncRNA pairs.
  • Reconstruction of regulatory networks and functional enrichment analysis.
  • Prognostic value assessment of identified biomarkers using patient survival data.

Main Results:

  • Identified numerous CNA-driven enhancer-gene and enhancer-lncRNA pairs specific to Basal-like, Her2, LumA, and LumB breast cancer subtypes.
  • Functional analysis revealed CNA-driven enhancers influence key signaling pathways (e.g., P53, MAPK) crucial for subtype progression.
  • Discovered prognostic biomarkers, including MUM1 and AC016876.1, and enhancer-related lncRNA-mRNA pairs, correlating with patient survival outcomes.

Conclusions:

  • CNAs within enhancers significantly contribute to breast cancer heterogeneity and progression.
  • Subtype-specific regulatory networks highlight the role of CNA-driven enhancers and lncRNA-mRNA interactions.
  • Identified enhancer-related genes and lncRNA-mRNA pairs serve as potential prognostic markers and therapeutic targets for breast cancer subtypes.