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.
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DOI：
10.1158/1078-0432.ccr-07-4372
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发表时间：
2008-08-01
期刊：
影响因子：
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通讯作者：
Cerutti JM
中科院分区：
文献类型：
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作者：
Oler G;Camacho CP;Hojaij FC;Michaluart P Jr;Riggins GJ;Cerutti JM
为了鉴定甲状腺乳头状癌（PTC）相关的转录本，我们比较了甲状腺肿瘤和正常甲状腺组织产生的三个SAGE文库的基因表达谱。使用定量PCR（qPCR）在一组57个甲状腺肿瘤中验证选定的转录物。一组独立的71个石蜡包埋切片用于免疫组织化学分析验证。为了确定PTC相关基因表达是否可以预测淋巴结受累，研究了130例原发性PTC（54例转移性和76例非转移性）的单独队列。将BRAFV 600 E突变状态与qPCR数据进行比较，以鉴定可能受异常BRAF-MEK-ERK信号传导调节的基因。我们鉴定并验证了新的PTC相关转录本。三个基因（CST 6，CXCL 14，DHRS 3）与PTC密切相关。CXCL 14的免疫组织化学分析证实了qPCR数据，并证明了PTC上皮细胞中的蛋白质表达。CST 6、CXCL 14、DHRS 3和SPP 1与PTC淋巴结转移相关，其中CST 6、CXCL 14和SPP 1与转移呈正相关，DHRS 3与转移呈负相关。最后，我们发现CST 6和CXCL 14表达与BRAFV 600 E突变状态之间存在强相关性，表明这些基因可能在BRAF激活后被诱导，因此可能位于BRAF/MEK/ERK信号通路的下游。CST 6、CXCL 14、DHRS 3和SPP 1可能在PTC的发病和进展中发挥作用，并可能成为PTC治疗的分子靶点。
To identify papillary thyroid carcinoma (PTC)-associated transcripts, we compared the gene expression profiles of three SAGE libraries generated from thyroid tumors and a normal thyroid tissue. 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 immunohistochemistry analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 non-metastatic) was investigated. The BRAFV600E mutational status was compared to qPCR data, to identify genes that might be regulated by abnormal BRAF—MEK—ERK signaling. We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, DHRS3) are strongly associated with PTC. Immunohistochemistry analysis of CXCL14 confirmed the qPCR data and demonstrated 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 expression being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAFV600E mutational status suggesting that these genes may be induced subsequently to BRAF activation and, therefore, may be downstream in the BRAF/MEK/ERK signaling pathway. CST6, CXCL14, DHRS3 and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for PTC therapy.