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Impact of Nuclear Factor Erythroid 2–Related Factor 2 in Hepatocellular Carcinoma: Cancer Metabolism and Immune Status

Impact of Nuclear Factor Erythroid 2–Related Factor 2 in Hepatocellular Carcinoma: Cancer... We examined phosphorylated nuclear factor erythroid 2–related factor 2 (P‐NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P‐NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD‐L1) expression. In this retrospective study, immunohistochemical staining of P‐NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine‐18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD‐L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2‐overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P‐NRF2. Positive P‐NRF2 expression was significantly associated with high alpha‐fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P‐NRF2 expression was an independent predictor for recurrence‐free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD‐L1 protein expression levels were increased through hypoxia‐inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P‐NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hepatology Communications Wolters Kluwer Health

Impact of Nuclear Factor Erythroid 2–Related Factor 2 in Hepatocellular Carcinoma: Cancer Metabolism and Immune Status

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References (57)

Publisher
Wolters Kluwer Health
Copyright
© 2022 by the American Association for the Study of Liver Diseases
ISSN
2471-254X
eISSN
2471-254X
DOI
10.1002/hep4.1838
Publisher site
See Article on Publisher Site

Abstract

We examined phosphorylated nuclear factor erythroid 2–related factor 2 (P‐NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P‐NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD‐L1) expression. In this retrospective study, immunohistochemical staining of P‐NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine‐18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD‐L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2‐overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P‐NRF2. Positive P‐NRF2 expression was significantly associated with high alpha‐fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P‐NRF2 expression was an independent predictor for recurrence‐free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD‐L1 protein expression levels were increased through hypoxia‐inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P‐NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity.

Journal

Hepatology Communications – Wolters Kluwer Health

Published: Apr 23, 2022

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