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Updated: Feb 20, 2026

Author Spotlight: Efficient Detection of Immune Cell-Infiltration in Cancer Tissues Using Fluorescent Immunohistochemistry
Published on: January 26, 2024
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.
Abstract:
During tumorigenesis and metastasis, cancer cells initiate antioxidant defense mechanisms to prevent irreversible damage, thereby sustaining tumor growth. The functionality of reactive oxygen species (ROS)-scavenging proteins is dependent on nicotinamide adenine dinucleotide phosphate (NADPH), which is regulated by specific metabolic enzymes, which are described as potential biomarkers of cancer aggressiveness. Immunohistochemistry (IHC) is one of the most accessible and widely utilized techniques to augment the pathological diagnosis of cancer. Hence, this review addresses the protein expression of NADPH-related enzymes, as assessed by IHC, and their associations with human cancer progression factors (overall survival, tumor staging, metastasis, and recurrence). Studies indicate that glucose-6-phosphate dehydrogenase (G6PD), along with malic enzymes and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), represents the most pertinent enzymes examined through IHC concerning cancer aggressiveness. The immunolabeling method produced consistent results for this group of enzymes, which might lead to successful application in predicting tumor prognosis. Other NADPH-related enzymes, such as glutamate dehydrogenase (GDH), aldehyde dehydrogenase 1 (ALDH1), and dihydrofolate reductase (DHFR), deserve more extensive investigation to elucidate their potential as cancer biomarkers via IHC.
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.
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