School of Medicine and Health Sciences Poster Presentations

Poster Number

142

Document Type

Poster

Publication Date

3-2016

Abstract

The currently accepted stepwise model of breast tumorigenesis assumes a gradual transition from normal breast epithelial cells to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS) and then to invasive ductal carcinoma (IDC). Percutaneous core needle biopsy (CNB) is the standard technique following an abnormal mammographic finding. However, CNB is less reliable in differentiating simple ADH (sADH) from ADH component coexisted with advanced lesions such as DCIS and/or IDC (cADH). Therefore, to identify and validate novel reliable molecular biomarkers is essential in order to improve the efficiency of therapeutic recommendations, as well as to minimize anxiety and unnecessary procedures.

miRNAs function as tumor suppressors or oncogenes and play a critical role in cancer initiation and progression by regulating their target genes. Unlike messenger RNAs (mRNAs), which could be easily degraded, miRNAs are found to be stable not only in body fluid, but also in Formalin-Fixed, Paraffin-Embedded (FFPE) tissues. The stability of miRNAs in FFPE and blood samples suggests that they may be the ideal biomarkers for the early diagnosis and prognosis of cancer, including breast cancer. The goal of this research is to use FFPE and blood samples from the two different groups of patients, analyze the candidate miRNAs to differentiating simple sADH from cADH.

In our published studies, we identified a series of miRNAs that are differentially expressed during stepwise transition of breast carcinogenesis, including miR-671-5p. In this study, we showed that the expression of miR-671-5p and miR-638 decreases in ADH, DCIS, and IDC compared with the matched adjacent normal tissues. In addition, we examined the candidate miRNA expression in two groups of ADH blood samples: 28 sADHs and 32 cADHs by qRT-PCR. We found that miR-671-5p expression was decreased in cADHs, but not in sADHs, compared with their matched normal controls. Our recent publication demonstrated that miR-671-5p functions as a tumor suppressor miRNA during breast cancer progression by regulating FOXM1 expression.

Using NanoString technology, we found another miRNA, miR-545-3p to be significantly overexpressed in cADHs compared with sADH. miR-545-3p is related to Snai2, which is a member of Snail family transcription factor, encoding a transcription repressor involving in epithelial-mesenchymal transitions (EMT). Our data suggest that miRNAs, such as miR-671-5p and miR-545-3p may be potential circulating biomarkers for early breast cancer detection following mammography and CNB.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Presented at: GW Research Days 2016

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Circulating miRNA Biomarkers in Early Breast Cancer Detection following Mammography

The currently accepted stepwise model of breast tumorigenesis assumes a gradual transition from normal breast epithelial cells to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS) and then to invasive ductal carcinoma (IDC). Percutaneous core needle biopsy (CNB) is the standard technique following an abnormal mammographic finding. However, CNB is less reliable in differentiating simple ADH (sADH) from ADH component coexisted with advanced lesions such as DCIS and/or IDC (cADH). Therefore, to identify and validate novel reliable molecular biomarkers is essential in order to improve the efficiency of therapeutic recommendations, as well as to minimize anxiety and unnecessary procedures.

miRNAs function as tumor suppressors or oncogenes and play a critical role in cancer initiation and progression by regulating their target genes. Unlike messenger RNAs (mRNAs), which could be easily degraded, miRNAs are found to be stable not only in body fluid, but also in Formalin-Fixed, Paraffin-Embedded (FFPE) tissues. The stability of miRNAs in FFPE and blood samples suggests that they may be the ideal biomarkers for the early diagnosis and prognosis of cancer, including breast cancer. The goal of this research is to use FFPE and blood samples from the two different groups of patients, analyze the candidate miRNAs to differentiating simple sADH from cADH.

In our published studies, we identified a series of miRNAs that are differentially expressed during stepwise transition of breast carcinogenesis, including miR-671-5p. In this study, we showed that the expression of miR-671-5p and miR-638 decreases in ADH, DCIS, and IDC compared with the matched adjacent normal tissues. In addition, we examined the candidate miRNA expression in two groups of ADH blood samples: 28 sADHs and 32 cADHs by qRT-PCR. We found that miR-671-5p expression was decreased in cADHs, but not in sADHs, compared with their matched normal controls. Our recent publication demonstrated that miR-671-5p functions as a tumor suppressor miRNA during breast cancer progression by regulating FOXM1 expression.

Using NanoString technology, we found another miRNA, miR-545-3p to be significantly overexpressed in cADHs compared with sADH. miR-545-3p is related to Snai2, which is a member of Snail family transcription factor, encoding a transcription repressor involving in epithelial-mesenchymal transitions (EMT). Our data suggest that miRNAs, such as miR-671-5p and miR-545-3p may be potential circulating biomarkers for early breast cancer detection following mammography and CNB.

 

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