Plasma metabolomic profile in prostatic intraepithelial neoplasia and prostate cancer and associations with the prostate-specific antigen and the Gleason score

Markin, Pavel A.; Brito, Alex; Moskaleva, Natalia E.; Ларцова, Е. В.; Shpot, Yevgeny V; Lerner, Yulia V.; Mikhajlov, Vasily Y.; Potoldykova, Natalia V.; Enikeev, D.; Frano, Michael R. La; Appolonova, Svetlana A.

doi:10.1007/s11306-020-01694-y

Cited by 14 publications

(8 citation statements)

References 43 publications

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“…Recently, in plasma metabolomic profiling by GC/MS, 4-HBA was found to discriminate between the control, prostatic intraepithelial neoplasia, and prostate cancer, and its levels increased with disease progression. In our study, 4-HBA had the highest concentration in PCa (Figure 3A), and based on previous studies, we explain that the levels of 4-HBA could be useful in determining the abnormal prostate metabolic profile [36].…”

Section: Comparison Of Differential Metabolites Levels Among Urological Cancers Using Univariate Statistical Analysissupporting

confidence: 82%

A Unique Urinary Metabolic Feature for the Determination of Bladder Cancer, Prostate Cancer, and Renal Cell Carcinoma

Kang

Kim

et al. 2021

Metabolites

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Prostate cancer (PCa), bladder cancer (BCa), and renal cell carcinoma (RCC) are the most prevalent cancer among urological cancers. However, there are no cancer-specific symptoms that can differentiate them as well as early clinical signs of urological malignancy. Furthermore, many metabolic studies have been conducted to discover their biomarkers, but the metabolic profiling study to discriminate between these cancers have not yet been described. Therefore, in this study, we aimed to investigate the urinary metabolic differences in male patients with PCa (n = 24), BCa (n = 29), and RCC (n = 12) to find the prominent combination of metabolites between cancers. Based on 1H NMR analysis, orthogonal partial least-squares discriminant analysis was applied to find distinct metabolites among cancers. Moreover, the ranked analysis of covariance by adjusting a potential confounding as age revealed that 4-hydroxybenzoate, N-methylhydantoin, creatinine, glutamine, and acetate had significantly different metabolite levels among groups. The receiver operating characteristic analysis created by prominent five metabolites showed the great discriminatory accuracy with AUC > 0.7 for BCa vs. RCC, PCa vs. BCa, and RCC vs. PCa. This preliminary study compares the metabolic profiles of BCa, PCa, and RCC, and reinforces the exploratory role of metabolomics in the investigation of human urine.

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Section: Comparison Of Differential Metabolites Levels Among Urological Cancers Using Univariate Statistical Analysissupporting

confidence: 82%

A Unique Urinary Metabolic Feature for the Determination of Bladder Cancer, Prostate Cancer, and Renal Cell Carcinoma

Kang

Kim

et al. 2021

Metabolites

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“… 48 , 49 The 20-HETE can activate multiple signal pathways in cancer, including intracellular protein kinases and chemokines. 50 , 51 Alterations in arachidonic acid metabolism have been reported in human cancer patients 52 and cancer models in laboratory rodents. 53 Our findings suggest the possibility of an accelerated utilization of arachidonic acid during the HFD-enhanced metastatic progression.…”

Section: Discussionmentioning

confidence: 99%

Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma

Yan

Rust

Sundaram

et al. 2022

Nutr Metab Insights

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Both clinical and laboratory studies have shown that monocyte chemotactic protein-1 (MCP-1) is involved in cancer spread. To understand the role of MCP-1 in metabolism in the presence of metastasis, we conducted an untargeted metabolomic analysis of primary metabolism on plasma collected from a study showing that MCP-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma (LLC) to the lungs in mice fed a high-fat diet (HFD). In a 2 × 2 design, wild-type (WT) or Mcp-1 knockout ( Mcp-1-/-) mice maintained on the AIN93G standard diet or HFD were subcutaneously injected with LLC cells to induce lung metastasis. We identified 87 metabolites for metabolomic analysis from this study. Amino acid metabolism was altered considerably in the presence of LLC metastases with the aminoacyl-tRNA biosynthesis pathways as the leading pathway altered. The HFD modified lipid and energy metabolism, evidenced by lower contents of arachidonic acid, cholesterol, and long-chain saturated fatty acids and higher contents of glucose and pyruvic acid in mice fed the HFD. These findings were supported by network analysis showing alterations in fatty acid synthesis and glycolysis/gluconeogenesis pathways between the 2 diets. Furthermore, elevations of the citrate cycle intermediates (citric acid, fumaric acid, isocitric acid, and succinic acid) and glyceric acid in Mcp-1-/- mice, regardless of diet, suggest the involvement of MCP-1 in mitochondrial energy metabolism during LLC metastasis. The present study demonstrates that MCP-1 deficiency and the HFD altered plasma metabolome in mice bearing LLC metastases. These findings can be useful in understanding the impact of obesity on prevention and treatment of cancer metastasis.

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“…Not only do these neuropeptides and neurotransmitters act as potential tumor biomarkers, but due to their described role in cancer progression they provide for easily testable therapeutic targets. 99 , 100 , 101 , 102 The existence of drugs approved for human use that target neuropeptide receptors allows for a faster transition from bench to bedside. A major drug category of focus in this endeavor has been beta‐blockers, which are adrenergic antagonists that block adrenergic receptor functions.…”

Section: Therapeutic Potential: Targeting Neural Involvement In Tumorsmentioning

confidence: 99%

Neural regulations of the tumor microenvironment

Restaino

Vermeer

2021

FASEB BioAdvances

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The identification of nerves in the tumor microenvironment has ushered in a new area of research in cancer biology. Numerous studies demonstrate the presence of various types of peripheral nerves (sympathetic, parasympathetic, sensory) within the tumor microenvironment; moreover, an increased density of nerves in the tumor microenvironment correlates with worse prognosis. In this review, we address the current understanding of nerve-mediated alterations of the tumor microenvironment and how they impact disease through a variety of processes including direct nerve-cancer cell communication, alteration of the infiltrative immune population, and alteration of stromal components.

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Plasma metabolomic profile in prostatic intraepithelial neoplasia and prostate cancer and associations with the prostate-specific antigen and the Gleason score

Cited by 14 publications

References 43 publications

A Unique Urinary Metabolic Feature for the Determination of Bladder Cancer, Prostate Cancer, and Renal Cell Carcinoma

A Unique Urinary Metabolic Feature for the Determination of Bladder Cancer, Prostate Cancer, and Renal Cell Carcinoma

Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma

Neural regulations of the tumor microenvironment

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