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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses
Dejun Shen1, Helena R Chang, Zugen Chen
1Gonda/UCLA Breast Cancer Research Laboratory, Department of Surgery, Revlon/UCLA Breast Center, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Abstract:
To test the efficacy of combined high-throughput analyses (HTA) in target gene identification, screening criteria were set using >fivefold difference by microarray and statistically significant changes (p<0.01) in SAGE and EST. Microarray analysis of two normal and seven breast cancer samples found 129 genes with >fivefold changes. Further SAGE and EST analyses of these genes identified four qualified genes, ERBB2, GATA3, AGR2, and ANXA1. Their expression pattern was validated by RT-PCR in both breast cell lines and tissue samples. Loss of ANXA1 in breast cancer was further confirmed at mRNA level by Human Breast Cancer Tissue Profiling Array and at protein level by immunohistochemical staining. This study demonstrated that combined HTA effectively narrowed the number of genes for further study, while retaining the sensitivity in identifying biologically important genes such as ERBB2 and ANXA1. A distinctive loss of ANXA1 in breast cancer suggests its involvement in maintaining normal breast biology.
Insights
Combined high-throughput analyses effectively identified key breast cancer genes like ERBB2 and ANXA1. A significant loss of ANXA1 in breast cancer suggests its role in normal breast biology.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- Identifying novel cancer-related genes is crucial for understanding disease mechanisms.
- High-throughput analyses (HTA) offer powerful tools for gene discovery.
- Combining different HTA methods can refine gene identification.
Purpose of the Study:
- To evaluate the effectiveness of integrated high-throughput analyses for identifying target genes in breast cancer.
- To pinpoint specific genes involved in breast cancer development and progression.
Main Methods:
- Utilized microarray, Serial Analysis of Gene Expression (SAGE), and expressed sequence tag (EST) analyses.
- Established screening criteria including >fivefold difference (microarray) and p<0.01 (SAGE, EST).
- Validated gene expression using reverse transcription-polymerase chain reaction (RT-PCR), tissue arrays, and immunohistochemistry.
Main Results:
- Microarray analysis identified 129 genes with >fivefold changes between normal and breast cancer samples.
- Combined HTA pinpointed four key genes: ERBB2, GATA3, AGR2, and ANXA1.
- Confirmed loss of ANXA1 expression at both mRNA and protein levels in breast cancer, suggesting a tumor-suppressive role.
Conclusions:
- Combined HTA is an efficient strategy for narrowing down candidate genes while maintaining sensitivity.
- ERBB2 and ANXA1 are identified as biologically significant genes in breast cancer.
- The distinct loss of ANXA1 in breast cancer indicates its potential involvement in maintaining normal breast tissue homeostasis.
