Prognostic significance of G6PD expression and localization in lung adenocarcinoma

Nagashio, Ryo; Oikawa, Shota; Yanagita, Kengo; Hagiuda, Daisuke; Kuchitsu, Yuki; Igawa, Satoshi; Naoki, Katsuhiko; Satoh, Yukitoshi; Ichinoe, Masaaki; Murakumo, Yoshiki; Saegusa, Makoto; Sato, Yuichi

doi:10.1016/j.bbapap.2018.05.005

Cited by 40 publications

(30 citation statements)

References 29 publications

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“…PPP in lung cancer. G6PD is overexpressed in non-small cell lung carcinoma (NSCLC) (96), and the survival rate of patients with overexpressed G6PD protein is significantly poorer compared with those of patients with no G6PD overexpression (97). In addition, G6PD inhibition enhances lung cancer cell sensitivity to cisplatin by inducing oxidative stress (98).…”

Section: Ppp In Malignant Tumorsmentioning

confidence: 99%

Crucial role of the pentose phosphate pathway in malignant tumors (Review)

2019

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Interest in cancer metabolism has increased in recent years. The pentose phosphate pathway (PPP) is a major glucose catabolism pathway that directs glucose flux to its oxidative branch and leads to the production of a reduced form of nicotinamide adenine dinucleotide phosphate and nucleic acid. The PPP serves a vital role in regulating cancer cell growth and involves many enzymes. The aim of the present review was to describe the recent discoveries associated with the deregulatory mechanisms of the PPP and glycolysis in malignant tumors, particularly in hepatocellular carcinoma, breast and lung cancer. Contents 1. Introduction 2. Glucose in the PPP 3. Glucose breakdown through glycolysis in the PPP 4. PPP in malignant tumors 5. Perspectives

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Section: Ppp In Malignant Tumorsmentioning

confidence: 99%

Crucial role of the pentose phosphate pathway in malignant tumors (Review)

2019

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“…G6PD, which is the principal rate-limiting enzyme of the PPP, is the main actor in PPP-mediated cancer progression (8,12). Furthermore, G6PD can cooperate with numerous signaling pathways in order to promote cancer, and G6PD was reported to be overexpressed in various types of tumor, including breast carcinoma, ccRCC and lung adenocarcinoma (13)(14)(15). Previous work from our laboratory described the prognostic significance of G6PD in ccRCC, and demonstrated its role in promoting tumor growth through positive feedback regulation of phospho-signal transducer and activator of transcription 3 (p-STAT3) (14,16).…”

Section: G6pd Facilitates Clear Cell Renal Cell Carcinoma Invasion Bymentioning

confidence: 99%

G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway

et al. 2020

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Glucose-6-phosphate dehydrogenase (G6PD) is crucial rate-limiting enzyme of the pentose phosphate pathway (PPP). G6PD dysregulation has been reported in various types of human cancer, and the role of G6PD in cancer progression was demonstrated in numerous studies. A previous study from our laboratory described the prognostic significance of G6PD in clear cell renal cell carcinoma (ccRCC), and demonstrated its proliferative role through positive feedback regulation of the phosphorylated form of signal transducer and activator of transcription 3. However, the role of G6PD in ccRCC invasion remains unclear. In the present study, reverse transcription-quantitative (RT-q) PCR, western blotting, enzyme activity assay, transwell assay and immunohistochemistry analysis in cell model, xenograft mice model and human specimen studies were performed to evaluate the role of G6PD in ccRCC invasion. The results from the present study demonstrated that G6PD may promote ccRCC cell invasive ability by increasing matrix metalloproteinase 2 (MMP2) mRNA and protein expression both in vitro and in vivo. In addition, a positive correlation between G6PD and MMP2 expression was demonstrated by RT-qPCR and western blotting in twenty pairs of ccRCC tumor specimens and matched adjacent normal tissues. Furthermore, G6PD promoted reactive oxygen species (ROS) generation and activated the MAPK signaling pathway in ccRCC cells. In addition, ROS significantly promoted the MAPK signaling pathway activation, which in turn contributed to MMP2 overexpression in ccRCC cells. In conclusion, the present study demonstrated that G6PD may facilitate ccRCC cell invasive ability by enhancing MMP2 expression through ROS-MAPK axis pathway.

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“…Therefore, G6PD is reported to be a prognostic marker. [27][28][29] Additionally, our recent study of MCC demonstrated that G6PD is not only a prognostic predictor, but also a useful marker for judging the potential immune activity of a tumor. Low expression of G6PD indicates high immune activity and may suggest a good response for immune checkpoint blockade therapy.…”

Section: Discussionmentioning

confidence: 99%

Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma

Nakamura

Nagase

Yoshimitsu

et al. 2020

J Immunother Cancer

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BackgroundMerkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for precisely estimating the vastly different patient outcomes. We performed RNA sequencing to evaluate the immune response and comprehensively estimate prognostic values of immunogenic factors in patients with MCC.MethodsWe collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC at 10 facilities. The mRNA was extracted from formalin-fixed paraffin-embedded tissues. Next-generation sequencing, immunohistochemical staining and blood serum tests were performed.ResultsNext-generation sequencing results classified MCC samples into two types: the ‘immune active type’ was associated with better clinical outcomes than the ‘cell division type’. Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene was highly significantly upregulated in the ‘cell division type’. Among 395 genes, G6PD expression correlated with the presence of lymph node or distant metastases during the disease course and significantly negatively correlated with PD-L1 expression. Immunohistochemical staining of G6PD also correlated with disease-specific survival and exhibited less heterogeneity compared with PD-L1 expression. G6PD activity could be measured by a blood serum test. The detection values significantly increased as the cancer stage progressed and significantly decreased after treatment.ConclusionsG6PD expression was an immunohistochemically and serum-detectable prognostic marker that negatively correlated with immune activity and PD-L1 levels, and could be used to predict the immunotherapy response.

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Prognostic significance of G6PD expression and localization in lung adenocarcinoma

Cited by 40 publications

References 29 publications

Crucial role of the pentose phosphate pathway in malignant tumors (Review)

Crucial role of the pentose phosphate pathway in malignant tumors (Review)

G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway

Glucose-6-phosphate dehydrogenase correlates with tumor immune activity and programmed death ligand-1 expression in Merkel cell carcinoma

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