Microarray and next-generation sequencing to analyse gastric cancer.

Gastric cancer is the second after lung cause of cancer-related mortality in the world. Early detection and treatment can lead to a long survival time. Recently microarrays and next generation sequencing (NGS) have become very useful tools of comprehensive research into gastric cancer, facilitating the identification of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discovery to practical clinical benefits. Although there are many biomarkers and target agents, only a minority of patients are tested and treated accordingly. Microarray technology with maturity was established more than 10 years ago, and has been widely used in the study of functional genomics, systems biology, and genomes in medicine. Second generation sequencing technology is more recent, but development is very fast, and it has been applied to the genome, including sequencing and epigenetics and many aspects of functional genomics. Here we review insights gained from these studies regarding the technology of microarray and NGS, how to elucidate the molecular basis of gastric cancer and identify potential therapeutic targets, and how to analyse candidate genes. We also discuss the challenges and future directions of such efforts.

PA28ß regulates cell invasion of gastric cancer via modulating the expression of chloride intracellular channel 1.

PA28ß is a subunit of proteasome activator PA28. Previous study suggests that PA28ß is involved in the invasiveness and metastasis of gastric adenocarcinoma (GA), however, the mechanism is not fully understood. In the present study, we showed that invasive abilities of gastric cancer cells were enhanced when PA28ß being down-regulated, and were inhibited when PA28ß being overexpressed. To explore the possible mechanism of PA28ß associated elevated invasiveness, the protein profiles of PA28ß knock down and parental negative control gastric cancer cells were compared using proteomics approach. The results revealed that there were 43 proteins were differentially expressed, among them, chloride intracellular channel 1 (CLIC1) was significantly up-regulated and selected for further functional study. Down-regulation of CLIC1 by RNA interference was able to markedly inhibit cell invasion of PA28ß knock down gastric carcinoma cells. In addition, an inverse correlation between PA28ß and CLIC1 expressions was also verified in GA tissue samples, suggesting that knockdown of PA28ß could enhance tumor invasion and metastasis, at least in part, through up-regulation of CLIC1. Our results provide novel insight into the mechanisms of PA28ß related invasiveness and metastasis of GA, and suggest new alternative approaches for GA treatment.