Alterations of Lipid Metabolism in Cancer: Implications in Prognosis and Treatment

Fernández, Lilia; Cedrón, Marta Gómez de; Molina, Ana Ramı́rez de

doi:10.3389/fonc.2020.577420

Cited by 131 publications

(121 citation statements)

References 298 publications

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“…The deregulated gene expression of certain lipid metabolism genes has been associated with altered cell metabolism and poor survival in several types of cancer and as a result they have been proposed as prognostic biomarkers [ 5 , 6 , 7 , 8 , 14 ]. We investigated the prognostic value of lipid metabolism genes in SCLC patients, by performing survival analysis based on gene expression.…”

Section: Resultsmentioning

confidence: 99%

“…Several enzymes related to lipid-metabolic pathways have been associated with cancer survival and proposed as biomarkers of cancer [ 8 ]. Here, we described a lipid GRS based on the expression of two lipid metabolism-related genes involved in the metabolic function of the cell: AMACR and PLIN1 .…”

Section: Discussionmentioning

confidence: 99%

“…PLIN1 expression has also been reported as a favorable marker of other types of cancer like breast cancer but not for SCLC [ 18 ]. The design, validation and use of genetic scores unlock new opportunities to incorporate precision approaches into clinical advice [ 8 ]. Notably, patients overexpressing AMACR and PLIN1 increased their survival time to almost 7 months.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to well-known Warburg effect, lipid metabolism contributes to cancer metabolic reprogramming [ 4 ]. Interestingly, lipid metabolism-related genes display remarkable roles as prognostic biomarkers in various types of cancer including non-small cell lung cancer [ 5 , 6 , 7 , 8 ]. However, and probably due to its low incidence and particular characteristics, the use of lipid metabolism-related genes to predict patient prognosis in SCLC remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Health Together with a Lipid Genetic Risk Score Predicts Survival of Small Cell Lung Cancer Patients

Fernández

Merino

Colmenarejo

et al. 2021

Cancers

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Small cell lung cancer (SCLC) prognosis is the poorest of all types of lung cancer. Its clinical management remains heterogeneous and therefore, the capability to predict survival would be of great clinical value. Metabolic health (MH) status and lipid metabolism are two relevant factors in cancer prevention and prognosis. Nevertheless, their contributions in SCLC outcome have not yet been analyzed. We analyzed MH status and a transcriptomic panel of lipid metabolism genes in SCLC patients, and we developed a predictive genetic risk score (GRS). MH and two lipid metabolism genes, racemase and perilipin 1, are biomarkers of SCLC survival (HR = 1.99 (CI95%: 1.11–3.61) p = 0.02, HR = 0.36 (CI95%: 0.19–0.67), p = 0.03 and HR = 0.21 (CI95%: 0.09–0.47), respectively). Importantly, a lipid GRS of these genes predict better survival (c-index = 0.691). Finally, in a Cox multivariate regression model, MH, lipid GRS and smoking history are the main predictors of SCLC survival (c-index = 0.702). Our results indicate that the control of MH, lipid gene expression and environmental factors associated with lifestyle is crucial for increased SCLC survival. Here, we propose for the first time, a metabolic precision approach for SCLC patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic Health Together with a Lipid Genetic Risk Score Predicts Survival of Small Cell Lung Cancer Patients

Fernández

Merino

Colmenarejo

et al. 2021

Cancers

Self Cite

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show abstract

“…NK cell FA and cholesterol synthesis through FA synthase and stearoyl-CoA desaturase-1 (FASN/SCD1), and 3-hydroxy-3-methylglutaryl-CoA synthase/acetyl-CoA acetyl-transferase 2 (Hmgcs1/Acat2) respectively, result in FA accumulation, which leads to immune signal activation [ 69 ]. SREBPs transcription factors regulate this immune signal activation by IL-2, as well as IL-12 present within the TME [ 70 , 71 ].…”

Section: Nutrients Affecting the Cellular Activity Of Immune Cellsmentioning

confidence: 99%

Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level?

Sayed

Haibe

Amhaz

et al. 2021

IJMS

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Immunotherapy has changed the treatment paradigm in multiple solid and hematologic malignancies. However, response remains limited in a significant number of cases, with tumors developing innate or acquired resistance to checkpoint inhibition. Certain “hot” or “immune-sensitive” tumors become “cold” or “immune-resistant”, with resultant tumor growth and disease progression. Multiple factors are at play both at the cellular and host levels. The tumor microenvironment (TME) contributes the most to immune-resistance, with nutrient deficiency, hypoxia, acidity and different secreted inflammatory markers, all contributing to modulation of immune-metabolism and reprogramming of immune cells towards pro- or anti-inflammatory phenotypes. Both the tumor and surrounding immune cells require high amounts of glucose, amino acids and fatty acids to fulfill their energy demands. Thus, both compete over one pool of nutrients that falls short on needs, obliging cells to resort to alternative adaptive metabolic mechanisms that take part in shaping their inflammatory phenotypes. Aerobic or anaerobic glycolysis, oxidative phosphorylation, tryptophan catabolism, glutaminolysis, fatty acid synthesis or fatty acid oxidation, etc. are all mechanisms that contribute to immune modulation. Different pathways are triggered leading to genetic and epigenetic modulation with consequent reprogramming of immune cells such as T-cells (effector, memory or regulatory), tumor-associated macrophages (TAMs) (M1 or M2), natural killers (NK) cells (active or senescent), and dendritic cells (DC) (effector or tolerogenic), etc. Even host factors such as inflammatory conditions, obesity, caloric deficit, gender, infections, microbiota and smoking status, may be as well contributory to immune modulation, anti-tumor immunity and response to immune checkpoint inhibition. Given the complex and delicate metabolic networks within the tumor microenvironment controlling immune response, targeting key metabolic modulators may represent a valid therapeutic option to be combined with checkpoint inhibitors in an attempt to regain immune function.

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As a matter of fat: Emerging roles of lipid‐sensitive E3 ubiquitin ligases

Gawden‐Bone,

Lehner,

Volkmar

2023

BioEssays

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The dynamic structure and composition of lipid membranes need to be tightly regulated to control the vast array of cellular processes from cell and organelle morphology to protein‐protein interactions and signal transduction pathways. To maintain membrane integrity, sense‐and‐response systems monitor and adjust membrane lipid composition to the ever‐changing cellular environment, but only a relatively small number of control systems have been described. Here, we explore the emerging role of the ubiquitin‐proteasome system in monitoring and maintaining membrane lipid composition. We focus on the ER‐resident RNF145 E3 ubiquitin ligase, its role in regulating adiponectin receptor 2 (ADIPOR2), its lipid hydrolase substrate, and the broader implications for understanding the homeostatic processes that fine‐tune cellular membrane composition.

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Alterations of Lipid Metabolism in Cancer: Implications in Prognosis and Treatment

Cited by 131 publications

References 298 publications

Metabolic Health Together with a Lipid Genetic Risk Score Predicts Survival of Small Cell Lung Cancer Patients

Metabolic Health Together with a Lipid Genetic Risk Score Predicts Survival of Small Cell Lung Cancer Patients

Metabolic Factors Affecting Tumor Immunogenicity: What Is Happening at the Cellular Level?

As a matter of fat: Emerging roles of lipid‐sensitive E3 ubiquitin ligases

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