Identification of Gene Signatures Used to Recognize Biological Characteristics of Gastric Cancer upon Gene Expression Data

Abstract

High-throughput gene expression microarrays can be examined by machine-learning algorithms to identify gene signatures that recognize the biological characteristics of specific human diseases, including cancer, with high sensitivity and specificity. A previous study compared 20 gastric cancer (GC) samples against 20 normal tissue (NT) samples and identified 1,519 differentially expressed genes (DEGs). In this study, Classification Information Index (CII), Information Gain Index (IGI), and RELIEF algorithms are used to mine the previously reported gene expression profiling data. In all, 29 of these genes are identified by all three algorithms and are treated as GC candidate biomarkers. Three biomarkers, COL1A2, ATP4B, and HADHSC, are selected and further examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) staining in two independent sets of GC and normal adjacent tissue (NAT) samples. Our study shows that COL1A2 and HADHSC are the two best biomarkers from the microarray data, distinguishing all GC from the NT, whereas ATP4B is diagnostically significant in lab tests because of its wider range of fold-changes in expression. Herein, a data-mining model applicable for small sample sizes is presented and discussed. Our result suggested that this mining model may be useful in small sample-size studies to identify putative biomarkers and potential biological features of GC.

ATP4B suppresses cell proliferation and migration via mitochondrial/p53/NF-κB pathway in gastric cancer

“…It has been reported that ATP4B, COL1A2 and HADHSC are the promising biomarkers [6][7][8]. ATP4B is diagnostically significant with apparent fold-changes in our previous study [9]. While exhibiting the potential power, there is no research report so far about the role of ATP4B expression in human cancers yet.…”

“…Gastric cancer is among the most common cancers gastrointestinal malignancies with few effective treatment strategies. Previous studies have reported that ATP4B is downexpressed in GC tissues related to poor prognosis in patients with GC [9,13,14]. However, there are few researches involving in the role of ATP4B in tumorigenesis and progression of human gastric cancer.…”

“…Analysis of the H+/K+-β-deficient mice indicated that ATP4B involved in the differentiation and development of mature parietal cells [12]. It has been reported that decreased ATP4B expression is detected in human GC tissues closely associated with poor prognosis of GC patients [9,13]. Our previous showed that ATP4B silence in GC may contribute to the intragenic DNA methylation and histone deacetylation [14].…”

ITRAQ-based Bioinformatics Analysis Reveals the Potential Anticancer Effects of ATP4B in Gastric Cancer

“…In accordance with this, autoantibodies against ATP4B are regarded as serological diagnostic markers for patients with autoimmune atrophic gastritis, which are linked to an increased risk for gastric cancer [13]. Additionally, previous bioinformatics data have suggested that decreased ATP4B expressed in human GC tissue was substantially correlated with poor overall survival in patients with GC [14,15]. Therefore, further investigation into biological function of ATP4B in GC may improve understanding of the molecular mechanisms responsible for providing novel therapeutic targets of GC.…”

“…The initiation and development of GC is a multi-stage, heterogeneous and multifactorial pathology process involving numerous genetic, epigenetic and environmental factors alterations [22]. Recently, studies have reported that the ATP4B gene is downregulated in GC, which plays a negative role in the progression of GC [6,15]. Restoring ATP4B expression in GC cells may heighten the inhibitory effects of chemotherapeutic drugs on GC cell growth [10].…”