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Identification of significant gene regulations for breast cancer from human tissues

ABSTRACT: To discover individual genes with potential diagnostic and therapeutic utilities, we use gene expression profiling from real patient tissues to identify significantly regulated genes out of a broad coverage of human transcriptome. We use Agilent gene expression microarray technologies to measure gene expressions of 32 cancerous and normal tissues from breast cancer patients. Total RNAs were extracted and analyzed using Agilent microarray technologies. The whole genome expression profiling has been proformed and several significantly differently expressed genes (such as HS3ST4, MMP1, MMP11) were quatified by qPCR to verify their up/down-regulations, leading to discovery of important genes related to breast cancer metastasis. We examined 32 human breast tissues of three different breast cancer subtypes (including Luminal A, Luminal B, Triple Negative) and normal controls to perform microarray gene expression profiling.

ORGANISM(S): Homo sapiens

SUBMITTER: Qi Xin

PROVIDER: S-ECPF-GEOD-57297 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BACKGROUND: Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression. METHODS: Samples of breast cancer tissues were obtained during surgical intervention, according to the bioethical recommendations, and cryo-preserved until used. Tissue extracts were submitted to proteomic preparations for 2D-IPG. Protein identification was performed by N-terminal sequencing and/or peptide mass finger printing. RESULTS: The majority of the detected S100 proteins were absent, or present at very low levels, in the non-tumoral tissues adjacent to the primary tumor. This finding strengthens the role of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo-preserved breast cancer tissues showed that some proteins were ubiquitously expressed in almost all patients while others appeared more sporadic. Most, if not all, of the detected S100 members appeared reciprocally correlated. Finally, from the perspective of biomarkers establishment, a promising finding was the observation that patients which developed distant metastases after a three year follow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group. CONCLUSIONS: This article reports for the first time the comparative proteomic screening of several S100 protein members among a large group of breast cancer patients. The results obtained strongly support the hypothesis that a significant deregulation of multiple S100 protein members is associated with breast cancer progression, and suggest that these proteins might act as potential prognostic factors for patient stratification. We propose that this may offer a significant contribution to the knowledge and clinical applications of the S100 protein family to breast cancer.

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Identification of significant gene regulations for breast cancer from human tissues

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