The Molecular Mechanism of Metabolic Remodeling in Lung Cancer

Chang, Ligong; Fang, Surong; Gu, Wei

doi:10.7150/jca.31406

Cited by 32 publications

(25 citation statements)

References 119 publications

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“…Because we now know the potential role of uric acid in cancer initiation and progression, there may also be uric acid-lowering drugs, which have the potential for treating cancer. It has been reported that metabolic remodeling plays an important role in the evolution of some cancers [65], so targeting different mechanisms in carcinogenesis using uric acid is consistent with the findings that uric acid lowering drugs are able to exert anticancer effects.…”

Section: Uric Acid-lowering Therapy and Its Ability To Lower Cancer Risksupporting

confidence: 85%

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Mi¹,

Gong²,

Sui³

2020

J. Cancer

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In recent years, metabolic syndrome (Mets) has been a hot topic among medical scientists. Mets has an intimate relationship with the incidence and development of various cancers. As a contributory factor of Mets, hyperuricemia actually plays an inseparable role in the formation of various metabolic disorders. Although uric acid is classically considered an antioxidant with beneficial effects, mounting evidence indicates that a high serum uric acid (SUA) level may serve as a pro-oxidant to generate inflammatory reactions and oxidative stress. In this review, we describe the unrecognized role of hyperuricemia in cancer development and summarize major mechanisms linking uric acid to carcinogenesis. Furthermore, we also discuss the potential mechanism of liver metastasis of cancer and list some types of uric acid-lowering agents, which may exert anticancer effects.

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Section: Uric Acid-lowering Therapy and Its Ability To Lower Cancer Risksupporting

confidence: 85%

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Mi¹,

Gong²,

Sui³

2020

J. Cancer

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“… 4 The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase kinase (MEK)/extracellular-regulated protein kinase (ERK)/5′ AMP-activated protein kinase (AMPK) pathways participate in the metabolic reprogramming of lung cancer, affecting endogenous fatty acid metabolism, glycolysis, and the tricarboxylic acid cycle and activating the proliferation, invasion, and metastasis of lung cancer as a result. 5 , 6 Metabolic reprogramming is becoming an important feature of tumor biology.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Implication of a Metabolism-Associated Gene Signature in Lung Adenocarcinoma

Chen

et al. 2020

Molecular Therapy - Oncolytics

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Lung cancer is the most common cancer worldwide, leading to high mortality each year. Metabolic pathways play a vital role in the initiation and progression of lung cancer. We aimed to establish a prognostic prediction model for lung adenocarcinoma (LUAD) patients based on a metabolism-associated gene (MTG) signature. Differentially expressed (DE)-MTGs were screened from The Cancer Genome Atlas (TCGA) LUAD cohorts. Univariate Cox regression analysis was performed on these DE-MTGs to identify genes significantly correlated with prognosis. Least absolute shrinkage and selection operator (LASSO) regression was performed on the resulting genes to establish an optimal risk model. Survival analysis was used to assess the prognostic ability of the model. The prognostic value of the gene signature was further validated in independent Gene Expression Omnibus (GEO) datasets. A gene signature with 13 metabolic genes was identified as an independent prognostic factor. Kaplan-Meier survival analysis demonstrated the good performance of the risk model in both TCGA training and GEO validation cohorts. Finally, a nomogram incorporating clinical parameters and the metabolic gene signature was constructed to help individualize outcome predictions. The calibration curves showed excellent agreement between the actual and predicted survival.

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“…Metabolic reprogramming is one of the hallmarks of cancer ( Faubert, Solmonson & DeBerardinis, 2020 ), which takes place from the onset and throughout the development of cancer ( Chang, Fang & Gu, 2020 ). It plays an important role in the progression, metastasis, depressed immunity, and therapy resistance of cancer ( Lane, Higashi & Fan, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of a six-gene metabolic signature predicting overall survival for patients with lung adenocarcinoma

Cao

Lü

et al. 2020

PeerJ

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Background Lung cancer is the leading cause of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) is one of the main subtypes of lung cancer. Hundreds of metabolic genes are altered consistently in LUAD; however, their prognostic role remains to be explored. This study aimed to establish a molecular signature that can predict the prognosis in patients with LUAD based on metabolic gene expression. Methods The transcriptome expression profiles and corresponding clinical information of LUAD were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) between LUAD and paired non-tumor samples were identified by the Wilcoxon rank sum test. Univariate Cox regression analysis and the lasso Cox regression model were used to construct the best-prognosis molecular signature. A nomogram was established comprising the prognostic model for predicting overall survival. To validate the prognostic ability of the molecular signature and the nomogram, the Kaplan–Meier survival analysis, Cox proportional hazards model, and receiver operating characteristic analysis were used. Results The six-gene molecular signature (PFKP, PKM, TPI1, LDHA, PTGES, and TYMS) from the DEGs was constructed to predict the prognosis. The molecular signature demonstrated a robust independent prognostic ability in the training and validation sets. The nomogram including the prognostic model had a greater predictive accuracy than previous systems. Furthermore, a gene set enrichment analysis revealed several significantly enriched metabolic pathways, which suggests a correlation of the molecular signature with metabolic systems and may help explain the underlying mechanisms. Conclusions Our study identified a novel six-gene metabolic signature for LUAD prognosis prediction. The molecular signature could reflect the dysregulated metabolic microenvironment, provide potential biomarkers for predicting prognosis, and indicate potential novel metabolic molecular-targeted therapies.

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The Molecular Mechanism of Metabolic Remodeling in Lung Cancer

Cited by 32 publications

References 119 publications

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Prognostic Implication of a Metabolism-Associated Gene Signature in Lung Adenocarcinoma

Identification of a six-gene metabolic signature predicting overall survival for patients with lung adenocarcinoma

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