Bulk and single-cell transcriptome profiling reveal the metabolic heterogeneity in human breast cancers

Yu, Tian-Jian; Ma, Ding; Liu, Yingying; Xiao, Yi; Gong, Yue; Jiang, Yi‐Zhou; Hu, Xin; Di, Gen-Hong

doi:10.1016/j.ymthe.2021.03.003

“…Breast cancer is highly heterogeneous with five different molecular subtypes identified (Basal, Luminal A, Luminal B, HER2 and Normal-like) and are known to be metabolically very heterogeneous as well 116 ⁠. A recent multi-omics study conducted on breast cancer samples also corroborated the intertumor metabolic heterogeneity, but could cluster the tumors into two categories: those that were highly glycolytic and associated with poor prognosis and those that preferentially used fatty acid oxidation or glutaminolysis and were associated with better prognosis 117 ⁠. We also observed high heterogeneity in expression in breast cancer and matched normal samples.…”

Section: Discussionmentioning

confidence: 91%

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Sheraj

¹

,

Güray

²

,

Banerjee

³

2021

Sci Rep

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Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.

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“…Breast cancer is highly heterogeneous with ve different molecular subtypes identi ed (Basal, Luminal A, Luminal B, HER2 and Normal-like) and are known to be metabolically very heterogeneous as well 116 . A recent multi-omics study conducted on breast cancer samples also corroborated the intertumor metabolic heterogeneity, but could cluster the tumors into two categories: those that were highly glycolytic and associated with poor prognosis and those that preferentially used fatty acid oxidation or glutaminolysis and were associated with better prognosis 117 . We also observed high heterogeneity in expression in breast cancer and matched normal samples.…”

Section: Discussionmentioning

confidence: 91%

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Sheraj

¹

,

Güray

²

,

Banerjee

³

2021

Preprint

View full text Add to dashboard Cite

Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.

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“…Metabolic reprogramming is a hallmark of malignancy ( Vaupel et al, 2019 ). A previous study shows that BC can be classified according to the metabolic profile as glucose-dependent with a poor prognosis or FAO- and glutamine-dependent with a good prognosis ( Yu et al, 2021 ). In addition, evidence showed that UCP1 inhibited glycolysis through an FBP1-dependent pathway ( Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of UCP1 and UCP2 as Potential Prognostic Markers in Breast Cancer: A Study Based on Immunohistochemical Analysis and Bioinformatics

Yu

¹

,

Shi

²

,

Wu

³

et al. 2022

Front. Cell Dev. Biol.

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Background: Uncoupling protein 1 (UCP1) and UCP2 are associated with tumor metabolism and immunity. However, the prognostic value and molecular mechanisms underlying their action in breast cancer (BC) remain unclear.Materials and methods: In TCGA-BRCA cohort, we investigated the expression characteristics of UCP mRNAs, analyzed their prognostic value by Kaplan-Meier survival analysis, their potential molecular functions by gene set enrichment analysis, and their relationship with immune infiltrating cell types using TIMER and CIBERSORT, along with the assessment of their association with mutational profiles. Kaplan-Meier survival analysis was performed for UCPs in our cohort and their association with BC thermogenesis was assessed by thermal tomography.Results: High expression of UCP1 and UCP2 were positive prognostic markers for BC. UCP1 was associated with the impaired glucose metabolism, while UCP2 with enhanced anti-tumor immunity. High expressions of UCP1 and UCP2 were associated with CDH1 mutations. High UCP1 expression was associated with a high rate of thermogenesis in BC.Conclusions: These results implied a key role of UCP1 and UCP2 in prognosis, metabolism, and immune infiltration in BC. Further investigation of the relevant molecular mechanisms may provide new strategies for BC treatment.

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Bulk and single-cell transcriptome profiling reveal the metabolic heterogeneity in human breast cancers

Cited by 69 publications

References 57 publications

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Identification of UCP1 and UCP2 as Potential Prognostic Markers in Breast Cancer: A Study Based on Immunohistochemical Analysis and Bioinformatics

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