Identification and analysis of dysregulated fatty acid metabolism genes in breast cancer subtypes

Yousuf, Umar; Sofi, Shazia; Makhdoomi, Aanisa; Mir, Manzoor Ahmad

doi:10.1007/s12032-022-01861-2

Cited by 23 publications

(7 citation statements)

References 40 publications

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“…Increasing interest in the relationship between systemic metabolism, tumor metabolism, immunometabolism, and cancer outcomes, alongside evolving technologies expanding both the available data and the community's ability to mine it to develop new insights. To that end, in this study, we utilized multiple publicly available breast cancer datasets, including "ACRIN-FLT-Breast (ACRIN 6688)", TCGA BRCA "Phenotypes", TCGA BRCA "IlluminaHiSeq", "TCGA TARGET GTEx", "Node-negative breast cancer (Desmedt 2007)", "ICGC (donor centric)", As opposed to genes or metabolic fluxes involved in glucose [24][25][26][27][28][29][30][31]or lipid metabolism [31][32][33][34][35][36][37][38][39], there exists a relative paucity of studies exploring the impact of expression of genes regulating amino acid uptake in breast cancer. Therefore, we elected to focus the current study on the expression of LAT1, which transports large amino acids including leucine, isoleucine, valine, phenylalanine, methionine, tyrosine, histidine, and tryptophan into the cell, and its relationships with body weight, tumor cell proliferation, and immune infiltration.…”

Section: Discussionmentioning

confidence: 99%

The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer

Ramshankar,

Liu,

Perry

2023

Preprint

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L-type Amino Acid Transporter 1 (LAT1) facilitates the uptake of specific essential amino acids, and due to this quality, it has been correlated to worse patient outcomes in various cancer types. However, the relationship between LAT1 and various clinical factors, including menopausal status, in mediating LAT1's prognostic effects remains incompletely understood. This is particularly true in the unique subset of tumors that are both obesity-associated and responsive to immunotherapy, including breast cancer. To close this gap, we employed 6 sets of transcriptomic data using the Kaplan-Meier model in the Xena Functional Genomics Explorer, demonstrating that higher LAT1 expression diminishes breast cancer patients' survival probability. Additionally, we analyzed 3'-Deoxy-3'-18F-Fluorothymidine positron emission tomography-computed tomography (18F-FLT PET-CT) images found on The Cancer Imaging Archive (TCIA). After separating all patients based on menopausal status, we correlated the measured 18F-FLT uptake with various clinical parameters quantifying body composition, tumor proliferation, and immune cell infiltration. By analyzing a wealth of deidentified, open-access data, the current study investigates the impact of LAT1 expression on breast cancer prognosis, along with the menopausal status-dependent associations between tumor proliferation, immunometabolism, and systemic metabolism.

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Section: Discussionmentioning

confidence: 99%

The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer

Ramshankar,

Liu,

Perry

2023

Preprint

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“…In addition to NSCLC, ACOX2 has also been shown to be dysregulated in various cancers, including breast cancer [ 86 , 87 ], prostate cancer [ 88 , 89 ], and hepatocellular carcinoma [ 90 ], and targeting peroxisomes is an emerging potential therapeutic approach including NSCLC [ 91 , 92 , 93 ].…”

Section: Overcoming Drug Resistance and The Future Of Kras Targetingmentioning

confidence: 99%

Treatment Strategies for KRAS-Mutated Non-Small-Cell Lung Cancer

O’Sullivan

Keogh

Henderson

et al. 2023

Cancers

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Activating mutations in KRAS are highly prevalent in solid tumours and are frequently found in 35% of lung, 45% of colorectal, and up to 90% of pancreatic cancers. Mutated KRAS is a prognostic factor for disease-free survival (DFS) and overall survival (OS) in NSCLC and is associated with a more aggressive clinical phenotype, highlighting the need for KRAS-targeted therapy. Once considered undruggable due to its smooth shallow surface, a breakthrough showed that the activated G12C-mutated KRAS isozyme can be directly inhibited via a newly identified switch II pocket. This discovery led to the development of a new class of selective small-molecule inhibitors against the KRAS G12C isoform. Sotorasib and adagrasib are approved in locally advanced or metastatic NSCLC patients who have received at least one prior systemic therapy. Currently, there are at least twelve KRAS G12C inhibitors being tested in clinical trials, either as a single agent or in combination. In this study, KRAS mutation prevalence, subtypes, rates of occurrence in treatment-resistant invasive mucinous adenocarcinomas (IMAs), and novel drug delivery options are reviewed. Additionally, the current status of KRAS inhibitors, multiple resistance mechanisms that limit efficacy, and their use in combination treatment strategies and novel multitargeted approaches in NSCLC are discussed.

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“…p53 transactivates key proteins in lipid catabolism, thereby depriving cancer cells of lipid. A study examining the expression pattern of fatty acid metabolism genes in breast cancer patients showed that patients with wild-type p53 had significantly increased levels of FABP4, PLIN1 and MGLL and decreased level of FABP5 compared with mutant p53 [42]. p53 regulates fatty acid metabolism by activating and regulating the expression of guanidinoacetate methyltransferase (GAMT), which promotes fatty acid oxidation (FAO) and creatine biosynthesis and plays an essential role in maintaining energy homeostasis during glucose deprivation [43].…”

Section: P53 Controls Lipid Metabolismmentioning

confidence: 99%

The crisscross between p53 and metabolism in cancer

Mao¹,

Jiang²

2023

ABBS

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As the guardian of the genome, p53 is well known for its tumor suppressor function in humans, controlling cell proliferation, senescence, DNA repair and cell death in cancer through transcriptional and non-transcriptional activities. p53 is the most frequently mutated gene in human cancer, but how its mutation or depletion leads to tumorigenesis still remains poorly understood. Recently, there has been increasing evidence that p53 plays a vital role in regulating cellular metabolism as well as in metabolic adaptation to nutrient starvation. In contrast, mutant p53 proteins, especially those harboring missense mutations, have completely different functions compared to wild-type p53. In this review, we briefly summarize what is known about p53 mediating anabolic and catabolic metabolism in cancer, and in particular discuss recent findings describing how metabolites regulate p53 functions. To illustrate the variability and complexity of p53 function in metabolism, we will also review the differential regulation of metabolism by wild-type and mutant p53.

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Identification and analysis of dysregulated fatty acid metabolism genes in breast cancer subtypes

Cited by 23 publications

References 40 publications

The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer

The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer

Treatment Strategies for KRAS-Mutated Non-Small-Cell Lung Cancer

The crisscross between p53 and metabolism in cancer

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