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首页> 外文期刊>Journal of genetics >Frequent alterations of SLIT2-ROBO1-CDC42 signalling pathway in breast cancer: clinicopathological correlation
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Frequent alterations of SLIT2-ROBO1-CDC42 signalling pathway in breast cancer: clinicopathological correlation

机译：SLIT2-ROBO1-CDC42信号通路在乳腺癌中的频繁变化：临床病理相关性

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The aim of the study was to understand the role of SLIT2-ROBO1/2-CDC42 signalling pathways in development of breast cancer (BC). Primary BC samples (n = 150), comprising of almost equal proportion of four subtypes were tested for molecular alterations of SLIT2, ROBO1, ROBO2 and CDC42, the key regulator genes of this pathway. Deletion and methylation frequencies of the candidate genes were seen in the following order: deletion, SLIT2 (38.6%) > ROBO1 (30%) > ROBO2 (7.3%); methylation, SLIT2 (63.3%) > ROBO1 (26.6%) > ROBO2 (9.3%). Majority (80%, 120/150) of the tumours showed alterations (deletion/methylation) in at least one of the candidate genes. Overall, alterations of the candidate genes were as follows: SLIT2, 75.3% (101/150); ROBO1, 45.3% (68/150); ROBO2, 15.3% (23/150). Significantly, higher alteration of SLIT2 locus was observed in triple negative breast cancer (TNBC) over HER2 subtype (P = 0.0014). Similar trend is also seen in overall alterations of SLIT2 and/or ROBO1, in TNBC than HER2 subtype (P = 0.0012); of SLIT2 and/or ROBO2 in TNBC than luminal A (P = 0.014) and HER2 subtype (P = 0.048). Immunohistochemical analysis of SLIT2, ROBO1/2 showed reduced expression, concordant with their molecular alterations. Also, high expression of total CDC42 (49/52; 94.2%) and reduced expression of phospho Serine-71 CDC42 (41/52; 78.8%) was observed. Coalterations of SLIT2 and/or ROBO1, SLIT2 and/or ROBO2 had significant association with reduced expression of phospho Serine-71 CDC42 (P = 0.0012-0.0038). Alterations of SLIT2 and/or ROBO1, reduced expression of phospho Serine-71 CDC42 predicted poor survival of BC patients. Results indicate the importance of SLIT2-ROBO1-CDC42 signalling pathway in predicting tumour progression.
机译：这项研究的目的是了解SLIT2-ROBO1 / 2-CDC42信号通路在乳腺癌（BC）发生中的作用。测试了主要BC样本（n = 150），其中包括几乎相等比例的四个亚型，检测该途径的关键调节基因SLIT2，ROBO1，ROBO2和CDC42的分子变化。候选基因的缺失和甲基化频率按以下顺序显示：缺失，SLIT2（38.6％）> ROBO1（30％）> ROBO2（7.3％）;甲基化，SLIT2（63.3％）> ROBO1（26.6％）> ROBO2（9.3％）。大多数肿瘤（80％，120/150）在至少一种候选基因中显示出改变（缺失/甲基化）。总体而言，候选基因的改变如下：SLIT2，75.3％（101/150）; ROBO1，45.3％（68/150）; ROBO2，15.3％（23/150）。值得注意的是，在三阴性乳腺癌（TNBC）中，观察到SLIT2基因座的变化高于HER2亚型（P = 0.0014）。与HER2亚型相比，TNBC中SLIT2和/或ROBO1的总体变化也有相似的趋势（P = 0.0012）。 TNBC中SLIT2和/或ROBO2的表达高于管腔A（P = 0.014）和HER2亚型（P = 0.048）。 SLIT2，ROBO1 / 2的免疫组织化学分析显示表达降低，与其分子变化一致。而且，观察到总CDC42的高表达（49/52; 94.2％）和磷酸丝氨酸71CDC42的表达降低（41/52; 78.8％）。 SLIT2和/或ROBO1，SLIT2和/或ROBO2的联盟与磷酸丝氨酸71 CDC42的表达降低显着相关（P = 0.0012-0.0038）。 SLIT2和/或ROBO1的改变，磷酸丝氨酸71 CDC42表达的降低预示了BC患者的不良生存。结果表明SLIT2-ROBO1-CDC42信号通路在预测肿瘤进展中的重要性。

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