Nine metabolic biomarkers can detect gastric cancer

Gastric cancer (GC) patients show an altered metabolic profile as compared with healthy individuals, a recent China study has found. A biomarker panel monitoring for nine metabolites can facilitate timely detection of GC.

As one of the most common malignancies, GC is the third leading cause of cancer-related deaths in China,” the researchers said.

“GC is asymptomatic in early stages, and the majority of GC mortality is due to delayed symptoms. It is an urgent task to find reliable biomarkers for the identification of GC in order to improve outcomes,” they added.

Initial unsupervised principal component analysis and supervised partial least squares discriminant analysis showed that 93 parameters, including amino acids, carnitine/acylcarnitines, and other such indicators, could distinguish the 144 enrolled GC patients (mean age 58.13 years) from 161 healthy controls (mean age 55.96 years). [Sci Rep 2022;12:14632]

Subsequent screening processes narrowed down the list of potentially predictive metabolites to 23, which were then subjected to stepwise logistic regression analysis. The final screening identified nine features which, when applied with corresponding weighting in a complex logistic regression model, could accurately distinguish GC patients from healthy control comparators.

The biomarkers were alanine, arginine, glycine, ornithine, tyrosine/citrulline ratio, valine/phenylalanine ratio, isovalerylcarnitine/propionylcarnitine ratio, hydroxybutyrylcarnitine, and decadienoylcarnitine.

Receiver operating characteristic curve analysis revealed that this nine-metabolite panel had an area under the curve (AUC) of 0.9586 (95 percent confidence interval [CI], 0.9384–0.9788) in the training set, coupled with a sensitivity of 0.8611 and specificity of 0.9565.

The researchers then conducted tenfold cross-validation by dividing all the training set samples into 10 sub-partitions, which were then used to assess the performance of the predictive model. In addition, 44 samples from 22 GC patients and 22 healthy controls were used as a separate test set to evaluate the diagnostic performance of the metabolic panel.

Cross-validation confirmed the findings from the initial training set and yielded an AUC of 0.9438, with sensitivity and specificity estimates of 0.8750 and 0.9006, respectively. Similarly, the nine-biomarker metabolic panel had high diagnostic value, with an AUC of 0.9318, sensitivity of 0.9545, and specificity of 0.8636.

“A high-performance biomarker panel consisting of Ala, Arg, Gly, Orn, Tyr/Cit, Val/Phe, C4-OH, C5/C3, C10:2 was identified and validated for separating patients with GC from healthy individuals,” the researchers said. “These results highlighted that the metabolite biomarker panel may act as a potential valuable tool to detect GC.”

Perturbations in the levels of the nine metabolites identified reflect the metabolic disruptions considered as a hallmark of cancer, the researchers added. In particular, they found that patients with GC experience disturbances in their amino acid and lipid metabolic pathways, which could have been caused by an imbalance in protein metabolism due to host-tumour interactions, and by the high metabolic requirements of a tumour. [Nat Commun 2017;8:15267]

“Identifying how metabolism shifts in patients with cancer can contribute to disease diagnosis and prediction,” the researchers said.

Future studies seeking to validate the present findings should also look at perturbations in gastritis, which is often precedes GC diagnoses, as well as recruit more patients with advanced GC to determine metabolic changes as the disease progresses.