Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas.
Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas.
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唾液腺样囊性和乳腺基底癌中的诊断SOX10基因特征。
DOI：
10.1038/bjc.2013.326
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发表时间：
2013-07-23
影响因子：
8.8
通讯作者：
Yarbrough WG
中科院分区：
文献类型：
--
作者：
Ivanov SV;Panaccione A;Nonaka D;Prasad ML;Boyd KL;Brown B;Guo Y;Sewell A;Yarbrough WG
涎腺腺样囊性癌是一种生长缓慢的恶性肿瘤，有复发和远处转移的倾向。基底样乳腺癌（BBC）是一种分子亚型，占乳腺癌的15-20%，与ACC具有组织学相似性和基底细胞标志物，缺乏ER（雌激素受体）、PR（孕酮受体）和HER 2（人表皮生长因子受体2）的表达，与ACC相似，主要转移至肺和脑。这两种癌症都缺乏靶向治疗，原因是对它们的分子驱动因素缺乏了解。基因表达谱，免疫组织化学染色，蛋白质印迹，RT-PCR，并在大量的癌症数据集的计算机分析，以确定新的标志物和潜在的治疗ACC和BBC的目标。对于基因签名的检测和比较，我们使用最近开发的基于网络的多实验矩阵工具进行共表达分析，用于可视化和秩聚合。在ACC和BBC中，我们确定了特征性和重叠的SOX 10基因签名，其中包含大量新的潜在分子标记。S 0X 10被验证为两种癌症的敏感诊断标志物，并且其表达与正常和恶性肌上皮/基底细胞相关。在ACC、BBC和黑色素瘤（MEL）中，SOX 10表达与ROPN 1B、GPM 6 B、COL 9A 3和MIA的表达强烈共分离。在ACC和乳腺癌中，SOX 10表达与FOXA 1呈负相关，FOXA 1是一种细胞身份标记物，也是管腔乳腺亚型的主要调节因子。在BBC细胞系上验证了SOX 10签名的几个保守元件（MIA、TRIM 2、ROPN 1和ROPN 1B）的诊断意义。ACC和BBC中的SOX 10表达似乎是具有基底/肌上皮特征的癌症的高度协调的转录程序特征的一部分。ACC/BBC和其他癌症，如神经母细胞瘤和MEL之间的比较，揭示了这些癌症可能与其细胞身份相关的潜在分子标记。SOX 10作为ACC和BBC的一种新的诊断标志物，为研究其分子病因学和细胞起源提供了重要的分子信息。鉴于SOX 10最近被描述为MEL的主要驱动因素，鉴定SOX 10签名的保守元件可能有助于更好地理解SOX 10相关信号传导和开发新的诊断和治疗工具。
Salivary adenoid cystic carcinoma (ACC) is an insidious slow-growing cancer with the propensity to recur and metastasise to distant sites. Basal-like breast carcinoma (BBC) is a molecular subtype that constitutes 15–20% of breast cancers, shares histological similarities and basal cell markers with ACC, lacks expression of ER (oestrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2), and, similar to ACC, metastasises predominantly to the lung and brain. Both cancers lack targeted therapies owing to poor understanding of their molecular drivers. Gene expression profiling, immunohistochemical staining, western blot, RT-PCR, and in silico analysis of massive cancer data sets were used to identify novel markers and potential therapeutic targets for ACC and BBC. For the detection and comparison of gene signatures, we performed co-expression analysis using a recently developed web-based multi-experiment matrix tool for visualisation and rank aggregation. In ACC and BBC we identified characteristic and overlapping SOX10 gene signatures that contained a large set of novel potential molecular markers. SOX10 was validated as a sensitive diagnostic marker for both cancers and its expression was linked to normal and malignant myoepithelial/basal cells. In ACC, BBC, and melanoma (MEL), SOX10 expression strongly co-segregated with the expression of ROPN1B, GPM6B, COL9A3, and MIA. In ACC and breast cancers, SOX10 expression negatively correlated with FOXA1, a cell identity marker and major regulator of the luminal breast subtype. Diagnostic significance of several conserved elements of the SOX10 signature (MIA, TRIM2, ROPN1, and ROPN1B) was validated on BBC cell lines. SOX10 expression in ACC and BBC appears to be a part of a highly coordinated transcriptional programme characteristic for cancers with basal/myoepithelial features. Comparison between ACC/BBC and other cancers, such as neuroblastomaand MEL, reveals potential molecular markers specific for these cancers that are likely linked to their cell identity. SOX10 as a novel diagnostic marker for ACC and BBC provides important molecular insight into their molecular aetiology and cell origin. Given that SOX10 was recently described as a principal driver of MEL, identification of conserved elements of the SOX10 signatures may help in better understanding of SOX10-related signalling and development of novel diagnostic and therapeutic tools.
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影响因子：
12.3
作者：
Adler P;Kolde R;Kull M;Tkachenko A;Peterson H;Reimand J;Vilo J
通讯作者：
Vilo J
影响因子：
4.1
作者：
Lacroix, M;Leclercq, G
通讯作者：
Leclercq, G
DOI：
10.1186/bcr2764
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Raouf A
通讯作者：
Raouf A
影响因子：
4.6
作者：
Drerup, Catherine M.;Wiora, Heather M.;Morris, Jill A.
通讯作者：
Morris, Jill A.
影响因子：
11.2
作者：
Fagiani, Ernesta;Giardina, Giuseppina;Lanfrancone, Luisa
通讯作者：
Lanfrancone, Luisa