An integrative approach identified genes associated with drug response in gastric cancer

Area of Science:

• Genomics
• Cancer Biology
• Bioinformatics

Background:

• Gastric cancer (GC) is a leading cause of cancer mortality globally.
• The molecular basis of GC carcinogenesis and drug resistance remains poorly understood.
• Identifying novel genes involved in GC development is crucial.

Purpose of the Study:

• To identify novel, differentially expressed genes in GC using integrated genomic and epigenomic data.
• To investigate the role of these genes in GC development and drug resistance.
• To explore the potential of identified genes as diagnostic or prognostic markers.

Main Methods:

• Analysis of genome-wide mRNA expression, DNA copy number alterations, and DNA methylation in 154 primary GC samples and 47 matched controls.
• Application of 'within' and 'between' statistical analysis to compare tumor and control tissues across platforms.
• Identification of 'multi-regulated genes' (MRGs) exhibiting combined genetic and epigenetic changes.

Main Results:

• 126 MRGs were identified, many located at GC-associated genomic loci.
• MRGs were significantly enriched for cancer, GC, and drug response pathways.
• Knockdown of DDX27, TH1L, or IDH3G sensitized GC cells to chemotherapy; RAI14 knockdown reduced proliferation.
• Overexpression of DDX27 decreased epirubicin-induced DNA damage and apoptosis.
• Increased DDX27 mRNA and protein levels were observed in early-stage GC, suggesting potential as a diagnostic/prognostic marker.

Conclusions:

• An integrative bioinformatics strategy successfully identified novel genes altered in GC.
• Identified genes, particularly DDX27, play a role in GC cell drug resistance and proliferation.
• DDX27 shows promise as a potential diagnostic and prognostic biomarker for gastric cancer.