Abstract A66: Comprehensive gene expression analysis of ductal carcinoma in situ (DCIS) progression to invasive breast cancer reveals potential biomarkers

e14731 Background: Ductal carcinoma in situ (DCIS) display favorable outcome while little is known about the factors associated with invasive recurrence. To identify better prognostic biomarkers we performed gene expression analysis followed by immunohistochemistry (IHC) staining validation. Methods: Differential gene expression analysis of 29 pure DCIS patients was performed using nanostring platform. RNA was extracted from paraffin blocks from age/size matched 11 recurrence-free and 18 invasive-recurrence cases (disease free interval > 5 years). Gene annotation enrichment analysis was done for differentially expressed genes (DEG) using DAVID. Eighty-two pure DCIS cases were selected for external validation by IHC staining. Allred score cutoff 1 was used for survival analysis. Results: Ninety-nine differentially expressed genes were found statistically significant (p-value < 0.05). Androgen receptor (AR) gene, which encodes a transcription factor AR, has recently been highlighted as a favorable prognostic marker and a therapeutic target in invasive tumor (fold change = - 1.35, p < 0.001). AR protein expression was externally validated by IHC staining of 82 pure DCIS cases (24 invasive-recurrence versus 58 recurrence-free). Similar to gene expression analysis result, patients with invasive recurrence showed lower AR staining score than recurrence-free patients (p = 0.007). Cox regression analysis showed lower AR level as an independent risk factor of long-term invasive recurrence (HR 7.43, 95%CI 1.50 – 36.62). Gene enrichment analysis revealed enrichment of kinase pathway and cell cycle pathway in recurred cases (Enrichment Score = 2.43, 2.41 respectively). Conclusions: DEG pattern was observed among pure DCIS cases. AR may serve as a prognostic biomarker and targeting kinase, cell proliferation may be effective for higher risk DCIS patients.

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DUCTAL CARCINOMA IN SITU AND INVASIVE BREAST CANCER-BASED DIFFERENTIAL GENE EXPRESSION STUDY FOR THERAPEUTIC DEVELOPMENT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2016.v9s3.14317 ◽

2016 ◽

Vol 9 (9) ◽

pp. 48

Author(s):

Harshitha Gopisetty Ramachandra ◽

Seethalakshmi Sakthivel ◽

Inamul Hasan Madar ◽

Iftikhar Aslam Tayubi ◽

Skm Habeeb

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Gene Expression Profiling ◽

Ductal Carcinoma In Situ ◽

Invasive Breast Cancer ◽

Expression Profiling ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Differential Gene

ABSTRACTObjective: Breast cancer is the second most common cancer in women globally. Multiple inherited mutations in genes are predominantly associatedwith breast cancer. The gene expression profiling of breast tumors generated by DNA microarray analysis provides molecular phenotyping thatdetermines and characterizes the classifications of these tumors.Methods: In this work, we used gene expression profiling of breast cancer samples from Gene Expression Omnibus (GEO) database. The datasetGSE41194, retrieved from GEO, was used to investigate differential gene expression in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).The dataset contains 26 DCIS and 24 IBC samples. The data were analyzed in R and Bioconductor. To normalize the data Robust Multiarray Average(RMA) method was applied, limma software was used to identify the differentially expressed genes (DEGs) in DCIS and IBC; an adjusted p value ≤0.05was used to filter differentially expressed probe sets, and a fold change (FC) ≥ 2 to identify upregulated and ≤−2 for downregulated genes. The DEGsretrieved were clustered and annotated using Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resourceswith an EASE score ≤0.1 and count 2.Results: The analysis obtained 72 DEGs with a p≤0.05. The FC≥2 identified 38 upregulated probesets and FC≤−2 identified 34 downregulated probesets. The up and downregulated genes obtained in various comparisons were characterized based on gene ontology (GO) and pathway analyses inDAVID, which retrieved six genes that had principal pathways targeting breast cancer.Conclusion: Identification of these genes and pathways enhances the knowledge and progression of DCIS to IBC; paving a novel way for developingnew therapies for treating patients with breast cancer.Keywords: Molecular phenotyping, Gene Expression, Ductal carcinoma in situ, Invasive breast cancer.

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