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

ABSTRACT: Cancer remains the second leading cause of mortality worldwide. In the course of this multistage and multifactorial disease, a set of alterations takes place, with genetic and environmental factors modulating tumorigenesis and disease progression. Metabolic alterations of tumors are well-recognized and are considered as one of the hallmarks of cancer. Cancer cells adapt their metabolic competences in order to efficiently supply their novel demands of energy to sustain cell proliferation and metastasis. At present, there is a growing interest in understanding the metabolic switch that occurs during tumorigenesis. Together with the Warburg effect and the increased glutaminolysis, lipid metabolism has emerged as essential for tumor development and progression. Indeed, several investigations have demonstrated the consequences of lipid metabolism alterations in cell migration, invasion, and angiogenesis, three basic steps occurring during metastasis. In addition, obesity and associated metabolic alterations have been shown to augment the risk of cancer and to worsen its prognosis. Consequently, an extensive collection of tumorigenic steps has been shown to be modulated by lipid metabolism, not only affecting the growth of primary tumors, but also mediating progression and metastasis. Besides, key enzymes involved in lipid-metabolic pathways have been associated with cancer survival and have been proposed as prognosis biomarkers of cancer. In this review, we will analyze the impact of obesity and related tumor microenviroment alterations as modifiable risk factors in cancer, focusing on the lipid alterations co-occurring during tumorigenesis. The value of precision technologies and its application to target lipid metabolism in cancer will also be discussed. The degree to which lipid alterations, together with current therapies and intake of specific dietary components, affect risk of cancer is now under investigation, and innovative therapeutic or preventive applications must be explored.

SUBMITTER: Fernandez LP

PROVIDER: S-EPMC7655926 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Fernández Lara P LP Gómez de Cedrón Marta M Ramírez de Molina Ana A

Frontiers in oncology 20201028

Cancer remains the second leading cause of mortality worldwide. In the course of this multistage and multifactorial disease, a set of alterations takes place, with genetic and environmental factors modulating tumorigenesis and disease progression. Metabolic alterations of tumors are well-recognized and are considered as one of the hallmarks of cancer. Cancer cells adapt their metabolic competences in order to efficiently supply their novel demands of energy to sustain cell proliferation and meta ...[more]

PMID: 33194695

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Project description:BackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature.MethodsFirst, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective.ConclusionA total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed.

Dataset Information

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

Publications

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

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