Identification of functional genes regulating gastric cancer progression using integrated bioinformatics analysis.

BACKGROUND

Gastric cancer (GC) is one of the most common cancers and has a poor prognosis. Treatment of GC has remained unchanged over the past few years.

AIM

To investigate the potential therapeutic targets and related regulatory biomarkers of GC.

METHODS

We obtained the public GC transcriptome sequencing dataset from the Gene Expression Omnibus database. The datasets contained 348 GC tissues and 141 healthy tissues. In total, 251 differentially expressed genes (DEGs) were identified, including 187 down-regulated genes and 64 up-regulated genes. The DEGs' enriched functions and pathways include Progesterone-mediated oocyte maturation, cell cycle, and oocyte meiosis, Hepatitis B, and the Hippo signaling pathway. Survival analysis showed that BUB1, MAD2L1, CCNA2, CCNB1, and BIRC5 may be associated with regulation of the cell cycle phase mitotic spindle checkpoint pathway. We selected 26 regulated genes with the aid of the protein-protein interaction network analyzed by Molecular Complex Detection.

RESULTS

We focused on three critical genes, which were highly expressed in GC, but negatively related to patient survival. Furthermore, we found that knockdown of BIRC5, TRIP13 or UBE2C significantly inhibited cell proliferation and induced cell apoptosis. In addition, knockdown of BIRC5, TRIP13 or UBE2C increased cellular sensitivity to cisplatin.

CONCLUSION

Our study identified significantly upregulated genes in GC with a poor prognosis using integrated bioinformatics methods.