Dr Anuradha Budhu from Maryland, USA combined gene expression and metabolic profiling analyses to identify factors associated with outcomes of patients with hepatocellular carcinoma.
The research team compared metabolic and gene expression patterns between paired tumor and nontumor tissues from 30 patients with hepatocellular carcinoma, and validated the results using samples from 356 patients with hepatocellular carcinoma.
The team reported that a total of 469 metabolites were measured using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry.
Metabolic and genomic data were integrated, and Kaplan–Meier and Cox proportional hazards analyses were used to associate specific patterns with patient outcomes.
The researchers found that the associated factors were evaluated for their effects on cancer cells in vitro and tumor formation in nude mice.
The research team identified 28 metabolites, and 169 genes associated with aggressive hepatocellular carcinoma.
The team of doctors noted that lipid metabolites of stearoyl-CoA-desaturase activity were associated with aberrant palmitate signaling in aggressive hepatocellular carcinoma samples.
|Lipid metabolites of stearoyl-CoA-desaturase activity were associated with aberrant palmitate signaling |
Expression of gene products associated with these metabolites, including stearoyl-CoA-desaturase, were associated independently with survival times and tumor recurrence in the test and validation sets.
The research team assessed that combined expression of stearoyl-CoA-desaturase and α-fetoprotein were associated with outcomes of patients with early-stage hepatocellular carcinoma.
Levels of monounsaturated palmitic acid, the product of stearoyl-CoA-desaturase activity, were increased in aggressive hepatocellular carcinoma.
The team found that monounsaturated palmitic acid increased migration and invasion of cultured hepatocellular carcinoma cells, and colony formation by hepatocellular carcinoma cells.
The team of doctors noted that hepatocellular carcinoma cells that expressed small interfering RNA against stearoyl-CoA-desaturase had decreased cell migration and colony formation in culture and reduced tumorigenicity in mice.
Dr Budhu's team concluded, "By using a combination of gene expression and metabolic profile analysis, the identified a lipogenic network that involves stearoyl-CoA-desaturase and palmitate signaling, and was associated with hepatocellular carcinoma progression and patient outcomes."
"The microarray platform and data have been submitted to the Gene Expression Omnibus public database at NCBI following MIAME guidelines."