Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients.
Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients.
复制标题
临床癌症患者中阿卡特-盾复合体样基因特征的系统分析。
DOI：
10.3892/mco.2016.1094
复制
发表时间：
2017-01
影响因子：
1.2
通讯作者：
Werb Z
中科院分区：
文献类型：
--
作者：
Wang CY;Shahi P;Huang JT;Phan NN;Sun Z;Lin YC;Lai MD;Werb Z
无壳-盾状复合物样（ASCL）家族，也称为“无壳-盾状复合物同系物”或“无壳-盾状家族碱性螺旋-环-螺旋转录因子”，对于神经系统的正常发育至关重要，并且ASCL的失调在精神和神经障碍中起关键作用。ASCL家族由5个成员组成，即ASCL 1、ASCL 2、ASCL 3、ASCL 4和ASCL 5。ASCL 1基因在肺癌发展过程中是一个潜在的癌基因。ASCL 2表达增加与结肠癌发展之间存在相关性。在异种移植肿瘤实验中，抑制ASCL 2减少了细胞增殖和肿瘤生长。虽然先前的研究表明ASCL 1和ASCL 2参与肿瘤的发展，但对其余的ASCL家族成员及其对肿瘤发生的潜在影响知之甚少。因此，研究ASCL家族基因在不同类型癌症中的表达的整体方法可能为癌症研究提供新的见解。在这项研究中，我们利用基于网络的微阵列数据库（Oncomine;）来分析ASCL家族在临床癌症和正常组织中的转录表达。我们的生物信息学分析揭示了多个ASCL家族成员在多种类型癌症的肿瘤发病和进展过程中的潜在参与。与正常组织相比，ASCL 1在肺癌、胰腺癌、肾癌、食道癌和头颈癌中表现出更高的表达，而ASCL 2在乳腺癌、结肠癌、胃癌、肺癌、头颈癌、卵巢癌和睾丸癌中表现出高表达。然而，ASCL 3仅在乳腺癌中表现出高表达。有趣的是，在黑色素瘤和膀胱癌、乳腺癌、胃癌和结肠癌中，ASCL 1表达下调。ASCL 2在肉瘤、黑素瘤、脑癌和前列腺癌中表现出低表达水平。在淋巴瘤、膀胱癌、宫颈癌、肾癌和上皮癌中检测到ASCL 3表达减少。类似地，ASCL 5在大多数脑癌亚型中表现出低表达，如胶质母细胞瘤和少突胶质细胞瘤。这项分析支持了特定ASCL成员可能在癌症发展中起重要作用的假设。总的来说，我们的数据表明ASCL基因家族成员表达的改变与癌症的发展相关。此外，ASCL家族成员根据癌症亚型进行分类。本报告的目的是为ASCL家族在各种癌症中的意义提供新的见解，我们的研究结果表明ASCL基因家族可能是未来癌症研究的理想靶点。
The achaete-scute complex-like (ASCL) family, also referred to as ‘achaete-scute complex homolog’ or ‘achaete-scute family basic helix-loop-helix transcription factor’, is critical for proper development of the nervous system and deregulation of ASCL plays a key role in psychiatric and neurological disorders. The ASCL family consists of five members, namely ASCL1, ASCL2, ASCL3, ASCL4 and ASCL5. The ASCL1 gene serves as a potential oncogene during lung cancer development. There is a correlation between increased ASCL2 expression and colon cancer development. Inhibition of ASCL2 reduced cellular proliferation and tumor growth in xenograft tumor experiments. Although previous studies demonstrated involvement of ASCL1 and ASCL2 in tumor development, little is known on the remaining ASCL family members and their potential effect on tumorigenesis. Therefore, a holistic approach to investigating the expression of ASCL family genes in diverse types of cancer may provide new insights in cancer research. In this study, we utilized a web-based microarray database (Oncomine; ) to analyze the transcriptional expression of the ASCL family in clinical cancer and normal tissues. Our bioinformatics analysis revealed the potential involvement of multiple ASCL family members during tumor onset and progression in multiple types of cancer. Compared to normal tissue, ASCL1 exhibited a higher expression in cancers of the lung, pancreas, kidney, esophagus and head and neck, whereas ASCL2 exhibited a high expression in cancers of the breast, colon, stomach, lung, head and neck, ovary and testis. ASCL3, however, exhibited a high expression only in breast cancer. Interestingly, ASCL1 expression was downregulated in melanoma and in cancers of the bladder, breast, stomach and colon. ASCL2 exhibited low expression levels in sarcoma, melanoma, brain and prostate cancers. Reduction in the expression of ASCL3 was detected in lymphoma, bladder, cervical, kidney and epithelial cancers. Similarly, ASCL5 exhibited low expression in the majority of brain cancer subtypes, such as glioblastoma and oligodendroglioma. This analysis supports the hypothesis that specific ASCL members may play an important role in cancer development. Collectively, our data suggest that alterations in the expression of ASCL gene family members are correlated with cancer development. Furthermore, ASCL family members were categorized according to cancer subtype. The aim of this report was to provide novel insights to the significance of the ASCL family in various cancers and our findings suggested that the ASCL gene family may be an ideal target for future cancer studies.