DACH1: its role as a classifier of long term good prognosis in luminal breast cancer.
DACH1: its role as a classifier of long term good prognosis in luminal breast cancer.
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DOI：
10.1371/journal.pone.0084428
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ball GR
中科院分区：
文献类型：
--
作者：
Powe DG;Dhondalay GK;Lemetre C;Allen T;Habashy HO;Ellis IO;Rees R;Ball GR
雌激素受体 (ER) 阳性（管腔）肿瘤在女性乳腺癌患者中所占比例最大。他们的疾病是一种异质性疾病，在治疗管理方面面临临床挑战。已经确定了三个主要的生物管腔组，但临床上可以将它们分为两个预后组，其中管腔 A 具有良好的预后，管腔 B 与不良预后相关。需要更多的生物标志物来达成分类共识。人工神经网络 (ANN) 等机器学习方法已用于利用高通量数据对乳腺癌生物标志物进行分类和识别。在这项研究中，我们使用人工神经网络 (ANN) 方法将 DACH1 识别为候选管腔标记物，并评估其在预测乳腺癌临床结果中的作用。使用结合网络推理算法的迭代 ANN 方法来识别公开可用的 cDNA 微阵列数据集中的 ER 相关生物标志物。 DACH1 被认为对 ER 相关标记有强烈影响，并且与 ER 呈正相关。通过对一系列未选择的乳腺癌（格式化为组织微阵列）进行免疫组织化学分析后的蛋白质表达水平进行统计评估，研究了其在预测乳腺癌特异性生存方面的临床相关性。强核 DACH1 染色在管状和小叶乳腺癌中更为常见。其表达与表达 PgR、上皮细胞角蛋白 (CK)18/19 和良好预后的“管腔样”标志物（包括 FOXA1 和 RERG）的 ER-α 阳性肿瘤相关（p<0.05）。在表现出更长的癌症特异性生存期和无病间隔以及转移形成减少的患者中，DACH1 增加 (p<0.001)。核 DACH1 显示与侵袭性生长和不良预后标志物呈负相关。核 DACH1 表达似乎是预测良好预后的 Luminal A 生物标志物，但并不独立于临床分期、肿瘤大小、NPI 状态或全身治疗。
Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs) have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN) approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER-associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK)18/19 and ‘luminal-like’ markers of good prognosis including FOXA1 and RERG (p<0.05). DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p<0.001). Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. Nuclear DACH1 expression appears to be a Luminal A biomarker predictive of good prognosis, but is not independent of clinical stage, tumour size, NPI status or systemic therapy.
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影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
8.4
作者：
Habashy, Hany Onsy;Powe, Desmond G.;Ellis, Ian O.
通讯作者：
Ellis, Ian O.
影响因子：
7.5
作者：
Lancashire, Lee J.;Rees, Robert C.;Ball, Graham R.
通讯作者：
Ball, Graham R.
影响因子：
3.8
作者：
Habashy, Hany Onsy;Powe, Desmond G.;Ellis, Ian O.
通讯作者：
Ellis, Ian O.
影响因子：
6.6
作者：
Gasparri, Fabio;Wang, Naining;Eriksson, Staffan
通讯作者：
Eriksson, Staffan