Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis

Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis

Author Oler, Gisele Autor UNIFESP Google Scholar
Camacho, Cleber P. Autor UNIFESP Google Scholar
Hojaij, Flavio C. Autor UNIFESP Google Scholar
Michaluart, Pedro Google Scholar
Riggins, Gregory J. Google Scholar
Cerutti, Janete M. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Johns Hopkins Univ
Abstract Purpose: To identify papillary thyroid carcinoma (PTC)-associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue.Experimental Design: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. the BRAF(V600E) mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling.Results: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAF(V600E) mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway.Conclusion: CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for FTC therapy.
Language English
Date 2008-08-01
Published in Clinical Cancer Research. Philadelphia: Amer Assoc Cancer Research, v. 14, n. 15, p. 4735-4742, 2008.
ISSN 1078-0432 (Sherpa/Romeo, impact factor)
Publisher Amer Assoc Cancer Research
Extent 4735-4742
Origin http://dx.doi.org/10.1158/1078-0432.CCR-07-4372
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000258217200010
URI http://repositorio.unifesp.br/handle/11600/30812

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