Dataset Information

Olfactory receptor gene abundance in invasive breast carcinoma.

ABSTRACT: Expression of olfactory receptors (ORs) has been reported in many human tissues outside the nasal epithelium. ORs have been validated as biomarkers in prostate cancer. In breast cancer, however, the expression and role of OR genes remain understudied. We examined the significance of OR transcript abundance in a large invasive breast carcinoma population and identified two OR genes, OR2W3 and OR2B6 to be potentially correlated to breast cancer progression. 960 breast invasive tumors and 56 human breast cancer cell lines were assessed for OR gene expression and 21 OR genes were highly abundant among 198 cases. Our transcriptome analysis discovered three significantly abundant OR genes among three sub-populations of invasive breast carcinoma patients. OR2W3 was correlated with invasion genes and basal-like subtype whereas OR2B6 was correlated with proliferation genes and luminal A subtype. Analyzing the OR gene upregulation among breast cancer cell lines showed that OR2B6 and OR2W3 were abundant similar to invasive breast tumors. Our study suggests that specific OR genes may be correlated with breast cancer characteristics, making ORs potential new diagnostic, and/or treatment markers. This study suggests future directions for the exploration of a role for ORs in the mechanisms of breast cancer proliferation and progression.

SUBMITTER: Masjedi S

PROVIDER: S-EPMC6760194 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Olfactory receptor gene abundance in invasive breast carcinoma.

Masjedi Shirin S Zwiebel Laurence J LJ Giorgio Todd D TD

Scientific reports 20190924 1

Expression of olfactory receptors (ORs) has been reported in many human tissues outside the nasal epithelium. ORs have been validated as biomarkers in prostate cancer. In breast cancer, however, the expression and role of OR genes remain understudied. We examined the significance of OR transcript abundance in a large invasive breast carcinoma population and identified two OR genes, OR2W3 and OR2B6 to be potentially correlated to breast cancer progression. 960 breast invasive tumors and 56 human ...[more]

PMID: 31551495

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Project description:BackgroundThe breast cancer is the most prevalent cancer among women, on the other hand absence of myoepithelial cells play a pivotal role in pathogenesis of this cancer. Thus we aimed to investigate the possible abilities of the molecular assay technique to find a relationship between mammary serine protease inhibitor (Maspin) gene expression possibly secreted by myoepithelial cells, grade of breast cancer and other prognostics factors (ER, PR, and c-erb-B2).MethodsParaffin embedded blocks of 31 breast cancer patients together with two normal breast tissues were used for IHC staining and Maspin gene RNA detection uses the real-time PCR method. Applying QIAGEN kit, we were able to measure Maspin RNA and Extract the cDNA of different samples for evaluating the Maspin RNA level.ResultsWe found that the RNA level was considerably lowerin these cancer samples compared with normal samples. In addition, different grades of breast cancer in the obtained results adopt some distinguishable values. The Maspin expression in samples with grades II and III is much lower than the ones in normal group (P<0.05) which could be considered as a promising way in diagnosing of this disease. The results showed no considerable differences in Maspin gene expression of the c-erb-B2 scores in the tumor group except the samples having score 0. The other observation of this research study confirmed that Maspin gene expression couldn't show any differences between the values of both ER and PR in different scores of the tumor group. On the other hand, the cDNA of these patients showed lower values compared with normal samples.ConclusionMaspin expression was reduced in samples with grade II& III of invasive ductal carcinoma. Based on expression of Maspin Inc-erb-B2, it seems that more expression happened in normal group comparing with different scores of it. We could suggest that there was a reverse relationship between tumor formation and Maspin gene expression. These results showed possible role of Maspin as prognostic factor.

Project description:Breast invasive carcinoma (BRCA) is the most malignant and leading cause of death in women. Global efforts are ongoing for improvement in early detection, prevention, and treatment. In this milieu, a comprehensive analysis of RNA-sequencing data of 1097 BRCA samples and 114 normal adjacent tissues is done to identify dysregulated genes in major molecular classes of BRCA in various clinical stages. Significantly enriched pathways in distinct molecular classes of BRCA have been identified. Pathways such as interferon signaling, tryptophan degradation, granulocyte adhesion & diapedesis, and catecholamine biosynthesis were found to be significantly enriched in Estrogen/Progesterone Receptor positive/Human Epidermal Growth Factor Receptor 2 negative, pathways such as RAR activation, adipogenesis, the role of JAK1/2 in interferon signaling, TGF-β and STAT3 signaling intricated in Estrogen/Progesterone Receptor negative/Human Epidermal Growth Factor Receptor 2 positive and pathways as IL-1/IL-8, TNFR1/TNFR2, TWEAK, and relaxin signaling were found in triple-negative breast cancer. The dysregulated genes were clustered based on their mutation frequency which revealed nine mutated clusters, some of which were well characterized in cancer while others were less characterized. Each cluster was analyzed in detail which led to the identification of NLGN3, MAML2, TTN, SYNE1, ANK2 as candidate genes in BRCA. They are central hubs in the protein-protein-interaction network, indicating their important regulatory roles. Experimentally, the Real-Time Quantitative Reverse Transcription PCR and western blot confirmed our computational predictions in cell lines. Further, immunohistochemistry corroborated the results in ~ 100 tissue samples. We could experimentally show that the NLGN3 & ANK2 have tumor-suppressor roles in BRCA as shown by cell viability assay, transwell migration, colony forming and wound healing assay. The cell viability and migration was found to be significantly reduced in MCF7 and MDA-MB-231 cell lines in which the selected genes were over-expressed as compared to control cell lines. The wound healing assay also demonstrated a significant decrease in wound closure at 12 h and 24 h time intervals in MCF7 & MDA-MB-231 cells. These findings established the tumor suppressor roles of NLGN3 & ANK2 in BRCA. This will have important ramifications for the therapeutics discovery against BRCA.

Dataset Information

Olfactory receptor gene abundance in invasive breast carcinoma.

Publications

Olfactory receptor gene abundance in invasive breast carcinoma.

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