NADPH-Related Enzymes and Cancer: Facts and Insights Into the Application of Immunohistochemistry

Camila M Scudeler1,2, Keila Samantha da Silva3, Rafaela V N Silva1,4

  • 1Department of Pathology, Genetics and Evolution, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil, uftm.edu.br.

PubMed

Insights

Cancer cells use antioxidant defenses, reliant on nicotinamide adenine dinucleotide phosphate (NADPH), to grow. This review examines NADPH-related enzymes via immunohistochemistry (IHC) as potential biomarkers for cancer aggressiveness and prognosis.

Area of Science:

  • Biochemistry
  • Oncology
  • Pathology

Background:

  • Cancer cells activate antioxidant defenses to survive and grow during tumorigenesis and metastasis.
  • Reactive oxygen species (ROS)-scavenging proteins require nicotinamide adenine dinucleotide phosphate (NADPH) for function.
  • NADPH metabolism is regulated by specific enzymes, identified as potential biomarkers for cancer aggressiveness.

Purpose of the Study:

  • To review protein expression of NADPH-related enzymes using immunohistochemistry (IHC).
  • To assess the association between these enzymes and cancer progression factors like survival, staging, metastasis, and recurrence.
  • To evaluate the potential of NADPH-related enzymes as prognostic biomarkers in human cancers.

Main Methods:

  • Literature review focusing on studies utilizing immunohistochemistry (IHC).
  • Analysis of protein expression of various NADPH-related metabolic enzymes in human cancers.
  • Correlation of enzyme expression levels with clinical parameters of cancer progression.

Main Results:

  • Glucose-6-phosphate dehydrogenase (G6PD), malic enzymes, and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) show consistent IHC results related to cancer aggressiveness.
  • These enzymes are identified as the most pertinent for IHC-based assessment of cancer prognosis.
  • Other enzymes like glutamate dehydrogenase (GDH), aldehyde dehydrogenase 1 (ALDH1), and dihydrofolate reductase (DHFR) require further investigation.

Conclusions:

  • IHC assessment of specific NADPH-related enzymes, particularly G6PD, malic enzymes, and MTHFD2, shows promise for predicting tumor prognosis.
  • These enzymes can serve as valuable biomarkers for cancer aggressiveness.
  • Further research is needed to explore the full potential of other NADPH-related enzymes as IHC biomarkers.