823 Pathway signatures in breast cancer progression − a genome-scale study based on integration of biology networks, DNA copy number, gene expression and mutations (original) (raw)

2010, European Journal of Cancer Supplements

Background: Thyroid nodules are clinically evident in about 5% of women and 1% of men therefore represent the most common endocrine pathology. Although more than 90% are benign a significant number undergo surgical excision. In 10% of all follicular patterned lesions diagnostic dilemma is presented in a subset of encapsulated lesions with partial nuclear features of papillary thyroid carcinoma and with histological features that fail to place them reliably in either the benign or the malignant category. Microarray gene profiling has shown a promise in the accurate discrimination of benign-malignant discrimination and molecular characterization of thyroid lesions. We focused on not particularly for significantly modulated candidate genes, but for sets of genes acting on similar antiapoptotic and signaling pathways. Materials and Methods: Tumour samples were obtained from 25 patients undergoing thyroid surgery and evaluated on histopathology prior to our experiments. Genomic RNA was isolated from the snap frozen tumour samples of follicular adenomas and sporadic type of papillary carcinomas. We used NimbleGen Human Expression 12X135K Arrays to analyze gene expression alterations between follicular thyroid adenoma and papillary thyroid carcinoma expression profiles. Quantitative RT-PCR and Western blot analysis were done in case of the 10 genes showing the highest expression changes on the array. Results: We found the consequent significant expression regulation of 378 genes 233 of them found to be significantly underexpressed in papillary carcinomas compared to the follicular adenoma tissues. Papillary thyroid carcinomas expressed modulated genes on the NFúB regulatory pathway. Nfúb itself was found to be up-regulated as well as its activator Med17 and the Eda1, the member of the TNF-related ligand family regulating epithelial development, wich has regulatory role in Nfúb-promoted transcription and Jnk signaling. additionally represented constitutive down-regulation Pparg and Mapk, 4, 8 and 10 partaking in NFúB inhibition, and Cyld1 over expression closely connected to NFúB signaling. Conclusions: Considering the fact that NFkB has already been found to be a promising diagnostic and therapeutic target, our investigation could provide new possibilities for diagnostic, therapeutic and preventative perspectives.

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