title: Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients.
abstract: 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; www.oncomine.org) 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.
authors.affiliation: Department of Anatomy, University of California, San Francisco, CA 94143, USA; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 11114, R.O.C.; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 11114, R.O.C.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Payam
authors.initials: P
authors.lastname: Shahi
authors.affiliation: Department of Oncology, University of California, San Francisco, CA 94143, USA.
authors.forename: John Ting Wei
authors.initials: JT
authors.lastname: Huang
authors.affiliation: Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh 7000, Vietnam; Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan 11114, R.O.C.
authors.forename: Nam Nhut
authors.initials: NN
authors.lastname: Phan
authors.affiliation: Department of Radiology, University of California, San Francisco, CA 94143, USA.
authors.forename: Zhengda
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan 11114, R.O.C.
authors.forename: Yen-Chang
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 11114, R.O.C.; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 11114, R.O.C.
authors.forename: Ming-Derg
authors.initials: MD
authors.lastname: Lai
authors.affiliation: Department of Anatomy, University of California, San Francisco, CA 94143, USA.
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
keywords: ASCL1; ASCL2; ASCL3; ASCL4; ASCL5; achaete-scute complex-like; cancer