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MicroRNA expression profiling of early primary breast cancer to identify prognostic markers and associated pathways

ABSTRACT: Retrospective series of primary breast cancer patients who received surgery between 1989 and 1992. Patients received adjuvant chemotherapy and/or adjuvant hormone therapy, or no adjuvant treatment. Tamoxifen was used as endocrine therapy for 5 years in ER+ BC patients. Patients who were <50 years of age, with lymph node positive tumors, or ER– and/or >3 cm in diameter, received adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for six cycles, in a thrice weekly intravenous regimen. Patients >50 years of age with ER–, lymph node–positive tumors also received CMF. Retrospective clinical study to identify breast cancer prognostic markers and associated pathways. 210 early primary breast cancers were considered who had complete 10-years follow-up, clinical and demographics information. miRNA profiling data.

ORGANISM(S): Homo sapiens

SUBMITTER: Buffa FM

PROVIDER: S-ECPF-GEOD-22216 | biostudies-other | 2011 Sep

REPOSITORIES: biostudies-other

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Project description:Breast cancer (BC) is the foremost cause of cancer-related deaths in women. BC patients are oftentimes presented with lymph node metastasis (LNM), which increases their risk of recurrence. Compelling data have recently implicated microRNAs in promoting BC metastasis. Therefore, the identification of microRNA (miRNA)-based molecular signature associated with LNM could provide an opportunity for a more personalized treatment for BC patients with high risk of LNM. In current study, we performed comprehensive miRNA profiling in matched primary breast and LNM and identified 40 miRNAs, which were differentially expressed in LNM compared to primary tumors. The expression of 14 miRNAs (Up: hsa-miR-155-5p, hsa-miR-150-5p, hsa-miR-146a-5p, hsa-miR-142-5p and down: hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-205-5p, hsa-miR-210-3p, hsa-miR-214-3p, hsa-miR-141-3p, hsa-miR-127-3p, hsa-miR-125a-5p, and hsa-let-7c-5p) was subsequently validated in a second cohort of 32 breast and 32 matched LNM tumor tissues. Mechanistically, forced expression of hsa-miR-205-5p, or hsa-miR-214-3p epigenetically inhibited MDA-MB-231 cell proliferation, colony formation, and cell migration. Global gene expression profiling on MDA-MB-231 cells overexpressing hsa-miR-205-5p, or hsa-miR-214-3p in combination with in silico target prediction and ingenuity pathway analyses identified multiple bona fide targets for hsa-miR-205-5p, hsa-miR-214-3p affecting cellular proliferation and migration. Interestingly, interrogation of the expression levels of hsa-miR-205 and hsa-miR-214 in the METABRIC breast cancer dataset revealed significantly poor overall survival in patients with downregulated expression of miR-205 [HR = 0.75 (0.61-0.91)], p = 0.003 and hsa-miR-214 [HR = 0.74 (0.59-0.93) p = 0.008]. Our data unraveled the miRNA-transcriptional landscape associated with LNM and provide novel insight on the role of several miRNAs in promoting BC LNM, and suggest their potential utilization in the clinical management of BC patients.

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MicroRNA expression profiling of early primary breast cancer to identify prognostic markers and associated pathways

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