Downregulation of nicotinamide nucleotide transhydrogenase and its naturally occurring antisense RNA in gastric cancer

Asia Pac J Clin Oncol. 2019 Oct;15(5):e191-e196. doi: 10.1111/ajco.13230. Epub 2019 Jul 16.

Abstract

Aim: Nicotinamide Nucleotide Transhydrogenase (NNT) gene encodes a protein, which is an important antioxidative enzyme that converts NADH to NADPH. This enzyme provides a significant proportion of the entire NADPH resource in the mitochondria. Previous reports have shown possible contribution of this gene in the carcinogenesis process.

Methods: In the current research, we evaluated expression levels of NNT gene and a naturally occurring antisense RNA (NNT-AS1) in gastric cancer specimens compared to their corresponding adjacent noncancerous tissues (ANCTs).

Results: Both NNT1 and NNT-AS1 genes were significantly downregulated in tumor tissues compared to ANCTs (expression ratio = 0.369, p = .045 and expression ratio = 0.368, p = .043, respectively). Transcript levels of NNT1 and NNT-AS1 were associated with the location of the primary tumor (p = .003 and .002, respectively). Moreover, expressions of both genes were significantly elevated in tumors with lymphatic/vascular invasion compared to tumors without lymphatic/vascular invasion (p = .001 and p = .005). No other remarkable associations were noticed between transcript levels of genes in tumor tissues and patients' information. Based on the area under curve (AUC) values in the receiver operating characteristic (ROC) curves, the diagnostic power of NNT1 and NNT-AS1 were estimated to be 0.62 and 0.63, respectively.

Conclusions: Although we demonstrated dysregulation of NNT1 and NNT-AS1 in gastric tumor specimens in association with clinical data of patients, these two genes are not supposed to be appropriate biomarkers for gastric cancer.

Keywords: NNT-AS; nicotinamide nucleotide transhydrogenase (NNT).

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • NADP Transhydrogenase, AB-Specific / genetics
  • NADP Transhydrogenase, AB-Specific / metabolism*
  • Prognosis
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Mitochondrial Proteins
  • RNA, Antisense
  • NADP Transhydrogenase, AB-Specific
  • NNT protein, human