Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer.

J Clin Lab Anal

Department of Biochemistry and Molecular Biology, School of Preclinical Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan Province, China.

Published: October 2022

AI Article Synopsis

  • The study focused on identifying new biomarkers for better detection of gastric cancer, specifically evaluating the proteins ornithine aminotransferase (OAT) and carbamoyl phosphate synthetase 1 (CPS1).
  • In a validation group, OAT showed a sensitivity of 70.4% and specificity of 80.5%, while CPS1 had a sensitivity of 68.6% and specificity of 73%, with their co-expression showing even better results at 81% sensitivity and 89% specificity.
  • The findings suggest that OAT and CPS1 are not only promising biomarkers for gastric cancer diagnosis but also correlate with the cancer's aggressive features, indicating potential implications for treatment strategies.

Article Abstract

Objective: The sensitivity and specificity of current biomarkers for gastric cancer were insufficient. The aim of the present study was to screen novel biomarkers and determine the diagnostic values of ornithine aminotransferase (OAT) and carbamoyl phosphate synthetase 1 (CPS1) for detecting gastric cancer.

Methods: With stable isotope tags, we labelled an initial discovery group of four paired gastric cancer tissue samples and identified with LC-ESI-MS/MS. A validation group of 159 gastric cancer samples and 30 healthy controls were used to validate the candidate targets. GSEA was used to explore the pathways activated in gastric cancer.

Results: Four hundred and thirty one proteins were found differentially expressed in gastric cancer tissues. Of these proteins, OAT and CPS1 were found over-expressed in gastric cancer patients, with sensitivity of 70.4% (95% CI: 63.3%-77.6%) and specificity of 80.5% (95% CI: 74.3%-86.7%) for ornithine aminotransferase, and with sensitivity of 68.6% (95% CI: 61.3%-75.8%) and specificity of 73% (95% CI: 66%-79.9%) for carbamoyl phosphate synthetase 1. The co-expression of OAT and CPS1 in gastric cancer tissues has a sensitivity of 81% (95% CI: 73.2%-88.8%) and specificity of 89% (95% CI: 83%-95%). Furthermore, both OAT and CPS1 were overexpressed in patients with local invasion T3 and T4 stages than those in patients with T1 and T2 stages. The co-expression of OAT and CPS1 was strongly correlated with histological grade I 68% (95% CI: 58.7%-77.3%) and TNM stage I/II 52% (95% CI: 42%-62%). The areas under ROC curves were up to 0.758 for the co-expression of OAT and CPS1 in gastric cancer. GSEA results showed that two gene sets and 30 gene sets were activated in OAT high- and CPS1 high-expression patients with gastric cancer, respectively.

Conclusions: The present findings indicated a tight correlation between the co-expression of OAT and CPS1 and the histological grade, local invasion, and TNM stages of gastric cancer. Therefore, OAT and CPS1 might be predictors for gastric cancer invasion and potential targets for anticancer drug design for gastric cancer.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551119PMC
http://dx.doi.org/10.1002/jcla.24692DOI Listing

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