Identification of Distinct Gene Expression Profiles between Esophageal Squamous Cell Carcinoma and Adjacent Normal Epithelial Tissues

Abstract

Esophageal squamous cell carcinoma (ESCC) is a predominant type of esophageal cancer, which is a malignant tumor originating from the esophageal mucosa or gland and is aggressive with poor prognosis. Identification of new gene expression patterns would be helpful for providing new targets for the early detection and treatment of ESCC patients. In the present study, we employed cDNA array technology to compare gene expression profiles between ESCC tissues and adjacent normal epithelial tissues from ESCC patients. There was at least a 4-fold change in the expression levels of 72 genes that were significantly increased and 107 genes that were decreased in ESCC compared with normal esophageal epithelium. Among them, genes known to be involved in ESCC were found, including matrix metalloproteinases, transcription factors SOX-4 and SOX-17, the Wingless-type MMTV integration site family member 2, and cell cycle regulators. Moreover, we have newly identified the two genes that are down-regulated in ESCC: monoamine oxidase A, an enzyme that catalyzes monoamines oxidation and 15-hydroxyprostaglandin dehydrogenase [NAD+], a prostaglandin-synthesizing enzyme that physiologically antagonizes COX-2. Likewise, we found the three genes that are up-regulated in ESCC: CD7, a cell surface glycoprotein member of the immunoglobulin superfamily, LIM-domain kinase 1, a small subfamily with an unique combination of two N-terminal LIM motifs and a C-terminal protein kinase domain, and TTK protein kinase, a previously unidentified member of the kinase family. These newly identified genes may be involved in the progression of the tumor and/or represent properties specific to ESCC.

Expression of cancer–testis antigens in esophageal cancer and their progress in immunotherapy

“…The gene expression profile data of Kono et al ( 2009 ) showed that TTK was overexpressed in a large portion (> 90%) of esophageal cancers, while it was almost undetectable in normal organs, except the testis and/or placenta. Similarly, two other studies have shown that TTK mRNA level is increased in esophageal cancer (Tao et al 2012 ; He et al 2018 ).…”

“…TTK protein kinase (TTK), also called Monopolar spindle 1 kinase (MPS1), is a HLA-A2402-restricted epitope peptide derived from cancer–testis antigens (CTA) (Mizukami et al 2008 ), and it is a previously unidentified member of the kinase family. It can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, and is associated with cell proliferation (Tao et al 2012 ) and cell invasion (King et al 2018 ). It is also a critical regulator of the spindle assembly checkpoint (SAC), which functions to maintain genomic integrity (Thu et al 2018 ) and controls cell fate (Szymiczek et al 2017 ).…”

HNF1A-AS1 promotes growth and metastasis of esophageal squamous cell carcinoma by sponging miR-214 to upregulate the expression of SOX-4

“…SOX4 also acted as a suppressor in the growth of glioblastoma, partly by activating p53-p21 signaling to induce G0/G1 cell cycle arrest (23). Moreover, SOX4 was found upregulated in ESCC and the SOX-Wnt interaction was identified to be involved in the development of ESCC (24). The specific regulatory mechanism remains to be further explored.…”

Key role of dual specificity kinase TTK in proliferation and survival of pancreatic cancer cells

“…The SAC thus serves as a safeguard against chromosome missegregation and subsequent aneuploidy. In an apparent contradiction to its role as a checkpoint protein, TTK has been shown to be overexpressed in breast cancer and other solid cancers ( Yuan et al , 2006 ; Salvatore et al , 2007 ; Daniel et al , 2011 ; Tao et al , 2012 ), and RNAi-mediated or pharmacological inhibition of TTK function efficiently attenuated growth of a variety of cancer cell lines ( Colombo et al , 2010 ; Tardif et al , 2011 ). Our own results demonstrate that this also holds true for pancreatic cancer.…”