A genomic approach to investigate expression profiles in Slovenian patients with gastric cancer

Abstract

Abstract. Despite its decreasing frequency in developed countries, gastric cancer remains a significant health burden. The aim of the present study was to construct cDNA libraries and analyze differentially expressed genes related to this disease. Gene expression profiles were generated with suppressive subtraction hybridization (SSH). We constructed eight SSH libraries, four representing up-regulated genes and four representing down-regulated genes in tumor tissues. Our approach revealed that several genes are abnormally expressed in gastric cancer. We also identified global deregulation of several pathways involved in the maintenance of normal gastric homeostasis. The results of this study support the view that, as a result of complex pathogenesis, diversity of genomic aberrations and multiplicity of carcinogenic causes, gastric cancer cannot be reduced to a single molecule. Our results may contribute new insight into molecular aspects of the disease and may prove advantageous for future development of therapeutic targets and diagnostic molecular markers.

Single nucleotide polymorphisms rs911160 in AURKA and rs2289590 in AURKB mitotic checkpoint genes contribute to gastric cancer susceptibility

“…It has been demonstrated that loss of BUB3 gene function could lead to chromosomal instability [Mendoza et al, 2005]. Interestingly, overexpression of BUB3 has also been described in gastric cancer [Grabsch et al, 2003;Hudler et al, 2011]. It has been demonstrated that there is a strong correlation between the level of BUB expression and tumor cell proliferation [Grabsch et al, 2003].…”

Genetic Aspects of Gastric Cancer Instability

“…Some of these pathways were initially discovered to be active during embryogenesis, but recent research showed that they are also involved in regeneration process of gastric mucosa [87]. As expected, global expression analyses showed aberrant expression of many genes, which differ among individuals, but are implicated in the same signalling networks [45, 87–91]. Furthermore, there is a complex interplay between environmental factors and these pathways that remains to be elucidated.…”

“…It was shown that AURKA overexpression overrides the mitotic spindle checkpoint and leads to incomplete cytokinesis, multinucleation, and multipolar spindles [ 43 , 44 ]. Other important regulators of cell cycle progression, such as CCNB1, CCNE1, PTTG1, and PLK, have also been found overexpressed in gastric carcinomas and associated with poor prognosis [ 45 – 48 ].…”

Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk

“… 1 , 2 It is believed that complex interplay of genetic and environmental factors triggers the accumulation of numerous genetic and epigenetic alterations in cells, resulting in deregulation of normal cell functions and disruption of stomach linen homeostasis. 3 - 6 Individual genetic factors probably contribute to aberrant processes in the genesis of malignant phenotype. Among them, single nucleotide polymorphisms (SNPs) and other genetic variants play an important role as the main genetic elements in the aetiology of several complex diseases, including gastric cancer.…”