Metabolites

Research

14 pages, 1848 KiB

Open AccessArticle

Urinary Volatomic Expression Pattern: Paving the Way for Identification of Potential Candidate Biosignatures for Lung Cancer

by Khushman Taunk, Priscilla Porto-Figueira, Jorge A. M. Pereira, Ravindra Taware, Nattane Luíza da Costa, Rommel Barbosa, Srikanth Rapole and José S. Câmara

Metabolites 2022, 12(1), 36; https://doi.org/10.3390/metabo12010036 - 4 Jan 2022

Cited by 4 | Viewed by 1835

Abstract

The urinary volatomic profiling of Indian cohorts composed of 28 lung cancer (LC) patients and 27 healthy subjects (control group, CTRL) was established using headspace solid phase microextraction technique combined with gas chromatography mass spectrometry methodology as a powerful approach to identify urinary [...] Read more.

The urinary volatomic profiling of Indian cohorts composed of 28 lung cancer (LC) patients and 27 healthy subjects (control group, CTRL) was established using headspace solid phase microextraction technique combined with gas chromatography mass spectrometry methodology as a powerful approach to identify urinary volatile organic metabolites (uVOMs) to discriminate among LC patients from CTRL. Overall, 147 VOMs of several chemistries were identified in the intervention groups—including naphthalene derivatives, phenols, and organosulphurs—augmented in the LC group. In contrast, benzene and terpenic derivatives were found to be more prevalent in the CTRL group. The volatomic data obtained were processed using advanced statistical analysis, namely partial least square discriminative analysis (PLS-DA), support vector machine (SVM), random forest (RF), and multilayer perceptron (MLP) methods. This resulted in the identification of nine uVOMs with a higher potential to discriminate LC patients from CTRL subjects. These were furan, o-cymene, furfural, linalool oxide, viridiflorene, 2-bromo-phenol, tricyclazole, 4-methyl-phenol, and 1-(4-hydroxy-3,5-di-tert-butylphenyl)-2-methyl-3-morpholinopropan-1-one. The metabolic pathway analysis of the data obtained identified several altered biochemical pathways in LC mainly affecting glycolysis/gluconeogenesis, pyruvate metabolism, and fatty acid biosynthesis. Moreover, acetate and octanoic, decanoic, and dodecanoic fatty acids were identified as the key metabolites responsible for such deregulation. Furthermore, studies involving larger cohorts of LC patients would allow us to consolidate the data obtained and challenge the potential of the uVOMs as candidate biomarkers for LC. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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15 pages, 1589 KiB

Open AccessArticle

Walker-256 Tumour-Induced Cachexia Altered Liver Metabolomic Profile and Function in Weanling and Adult Rats

by Natália Angelo da Silva Miyaguti, Gabriela de Matuoka e Chiocchetti, Carla de Moraes Salgado, Leisa Lopes-Aguiar, Lais Rosa Viana, Lea Blanchard, Rogério Willians dos Santos and Maria Cristina Cintra Gomes-Marcondes

Metabolites 2021, 11(12), 831; https://doi.org/10.3390/metabo11120831 - 1 Dec 2021

Cited by 2 | Viewed by 2588

Abstract

Cancer cachexia occurs in up to 85% of advanced cancer patients, affecting different tissues and organs, mainly the liver, which plays a central role in body metabolism control. However, liver responses to cancer cachexia progression are still poorly understood. Considering the possible different [...] Read more.

Cancer cachexia occurs in up to 85% of advanced cancer patients, affecting different tissues and organs, mainly the liver, which plays a central role in body metabolism control. However, liver responses to cancer cachexia progression are still poorly understood. Considering the possible different challenges provided by the rodent’s phase of life and the cachexia progression, we evaluated the liver metabolic alterations affected by Walker-256 tumour growth in weanling and young-adult rats. For this, we applied a metabolomics approach associated with protein and gene expression analyses. Higher amino acid levels and impaired glucose metabolism were important features in tumour-bearing animals’ liver tissue. The weanling hosts had more pronounced cachexia, with higher carcass spoliation, liver lipid metabolism and impaired CII and CIV mitochondrial complexes. The liver alterations in young adult tumour-bearing rats were related to energy status and nucleotide metabolites, such as uridine, NAD+, xanthosine, hypoxanthine and inosine. In conclusion, the Walker-256 tumour-induced cachexia impaired liver metabolism, being more severe in the weanling hosts. Further studies are needed to correlate these changes in the preclinical model, which can be correlated to the clinical features of cancer cachexia, allowing for a translational potential involving the liver function and its responses to potential treatments. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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11 pages, 3453 KiB

Open AccessArticle

Targeted Quantification of Carbon Metabolites Identifies Metabolic Progression Markers and an Undiagnosed Case of SDH-Deficient Clear Cell Renal Cell Carcinoma in a German Cohort

by Doreen William, Kati Erdmann, Jonas Ottemöller, Anastasios Mangelis, Catleen Conrad, Mirko Peitzsch, Evelin Schröck, Graeme Eisenhofer, Aristeidis Zacharis, Susanne Füssel, Daniela Aust, Barbara Klink and Susan Richter

Metabolites 2021, 11(11), 764; https://doi.org/10.3390/metabo11110764 - 9 Nov 2021

Cited by 1 | Viewed by 1972

Abstract

Renal cell carcinoma (RCC) is among the 10 most common cancer entities and can be categorised into distinct subtypes by differential expression of Krebs cycle genes. We investigated the predictive value of several targeted metabolites with regards to tumour stages and patient survival [...] Read more.

Renal cell carcinoma (RCC) is among the 10 most common cancer entities and can be categorised into distinct subtypes by differential expression of Krebs cycle genes. We investigated the predictive value of several targeted metabolites with regards to tumour stages and patient survival in an unselected cohort of 420 RCCs. Unsupervised hierarchical clustering of metabolite ratios identified two main clusters separated by α-ketoglutarate (α-KG) levels and sub-clusters with differential levels of the oncometabolite 2-hydroxyglutarate (2HG). Sub-clusters characterised by high 2HG were enriched in higher tumour stages, suggesting metabolite profiles might be suitable predictors of tumour stage or survival. Bootstrap forest models based on single metabolite signatures showed that lactate, 2HG, citrate, aspartate, asparagine, and glutamine better predicted the cancer-specific survival (CSS) of clear cell RCC patients, whereas succinate and α-ketoglutarate were better CSS predictors for papillary RCC patients. Additionally, this assay identifies rare cases of tumours with SDHx mutations, which are caused predominantly by germline mutations and which predispose to development of different neoplasms. Hence, analysis of selected metabolites should be further evaluated for potential utility in liquid biopsies, which can be obtained using less invasive methods and potentially facilitate disease monitoring for both patients and caregivers. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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18 pages, 2317 KiB

Open AccessArticle

A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

by Gabriela de Matuoka e Chiocchetti, Leisa Lopes-Aguiar, Natália Angelo da Silva Miyaguti, Lais Rosa Viana, Carla de Moraes Salgado, Ophelie Ocean Orvoën, Derly Florindo, Rogério Williams dos Santos and Maria Cristina Cintra Gomes-Marcondes

Metabolites 2021, 11(6), 404; https://doi.org/10.3390/metabo11060404 - 20 Jun 2021

Cited by 8 | Viewed by 2505

Abstract

Cancer cachexia is a severe wasting condition that needs further study to find ways to minimise the effects of damage and poor prognosis. Skeletal muscle is the most impacted tissue in cancer cachexia; thus, elucidation of its metabolic alterations could provide a direct [...] Read more.

Cancer cachexia is a severe wasting condition that needs further study to find ways to minimise the effects of damage and poor prognosis. Skeletal muscle is the most impacted tissue in cancer cachexia; thus, elucidation of its metabolic alterations could provide a direct clue for biomarker research and be applied to detect this syndrome earlier. In addition, concerning the significant changes in the host metabolism across life, this study aimed to compare the metabolic muscle changes in cachectic tumour-bearing hosts at different ages. We performed ¹H-NMR metabolomics in the gastrocnemius muscle in weanling and young adult Walker-256 tumour-bearing rats at different stages of tumour evolution (initial, intermediate, and advanced). Among the 49 metabolites identified, 24 were significantly affected throughout tumour evolution and 21 were significantly affected regarding animal age. The altered metabolites were mainly related to increased amino acid levels and changed energetic metabolism in the skeletal muscle, suggesting an expressive catabolic process and diverted energy production, especially in advanced tumour stages in both groups. Moreover, these changes were more severe in weanling hosts throughout tumour evolution, suggesting the distinct impact of cancer cachexia regarding the host’s age, highlighting the need to adopting the right animal age when studying cancer cachexia. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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15 pages, 1288 KiB

Open AccessArticle

Discovery of Volatile Biomarkers for Bladder Cancer Detection and Staging through Urine Metabolomics

by Joana Pinto, Ângela Carapito, Filipa Amaro, Ana Rita Lima, Carina Carvalho-Maia, Maria Conceição Martins, Carmen Jerónimo, Rui Henrique, Maria de Lourdes Bastos and Paula Guedes de Pinho

Metabolites 2021, 11(4), 199; https://doi.org/10.3390/metabo11040199 - 26 Mar 2021

Cited by 28 | Viewed by 2778

Abstract

Timely diagnosis is crucial to improve the long-term survival of bladder cancer (BC) patients. The discovery of new BC biomarkers based in urine analysis is very attractive because this biofluid is in direct contact with the inner bladder layer, in which most of [...] Read more.

Timely diagnosis is crucial to improve the long-term survival of bladder cancer (BC) patients. The discovery of new BC biomarkers based in urine analysis is very attractive because this biofluid is in direct contact with the inner bladder layer, in which most of the neoplasms develop, and is non-invasively collected. Hence, this work aimed to unveil alterations in the urinary volatile profile of patients diagnosed with BC compared with cancer-free individuals, as well as differences among patients diagnosed at different tumor stages, to identify candidate biomarkers for non-invasive BC diagnosis and staging. Urine analysis was performed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results unveiled that BC patients have a distinct urinary volatile profile characterized by higher levels of several alkanes and aromatic compounds, and lower levels of aldehydes, ketones and monoterpenes. Seventeen significantly altered volatiles were used to evaluate the performance for overall BC detection, disclosing 70% sensitivity, 89% specificity and 80% accuracy. Moreover, distinct urinary volatile profiles were found among patients diagnosed at different tumor stages (Ta/Tis, T1 and ≥T2). This work identified distinct urinary volatile signatures of BC patients with potential for non-invasive detection and staging of bladder cancer. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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12 pages, 1649 KiB

Open AccessArticle

Profiling of Metabolic Differences between Hematopoietic Stem Cells and Acute/Chronic Myeloid Leukemia

by Byung Hoo Song, Su Young Son, Hyun Kyu Kim, Tae Won Ha, Jeong Suk Im, Aeli Ryu, Hyeji Jeon, Hee Yong Chung, Jae Sang Oh, Choong Hwan Lee and Man Ryul Lee

Metabolites 2020, 10(11), 427; https://doi.org/10.3390/metabo10110427 - 26 Oct 2020

Cited by 6 | Viewed by 2537

Abstract

Although many studies have been conducted on leukemia, only a few have analyzed the metabolomic profiles of various leukemic cells. In this study, the metabolomes of THP-1, U937, KG-1 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia, CML), and cord blood-derived CD34-positive hematopoietic [...] Read more.

Although many studies have been conducted on leukemia, only a few have analyzed the metabolomic profiles of various leukemic cells. In this study, the metabolomes of THP-1, U937, KG-1 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia, CML), and cord blood-derived CD34-positive hematopoietic stem cells (HSC) were analyzed using gas chromatography-mass spectrometry, and specific metabolic alterations were found using multivariate statistical analysis. Compared to HSCs, leukemia cell metabolomes were found to have significant alterations, among which three were related to amino acids, three to sugars, and five to fatty acids. Compared to CML, four metabolomes were observed specifically in AML. Given that overall more metabolites are present in leukemia cells than in HSCs, we observed that the activation of glycolysis and oxidative phosphorylation (OXPHOS) metabolism facilitated the incidence of leukemia and the proliferation of leukemic cells. Analysis of metabolome profiles specifically present in HSCs and leukemia cells greatly increases our basic understanding of cellular metabolic characteristics, which is valuable fundamental knowledge for developing novel anticancer drugs targeting leukemia metabolism. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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Review

Jump to: Research, Other

28 pages, 1452 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Advances and Perspectives in Prostate Cancer Biomarker Discovery in the Last 5 Years through Tissue and Urine Metabolomics

by Ana Rita Lima, Joana Pinto, Filipa Amaro, Maria de Lourdes Bastos, Márcia Carvalho and Paula Guedes de Pinho

Metabolites 2021, 11(3), 181; https://doi.org/10.3390/metabo11030181 - 19 Mar 2021

Cited by 41 | Viewed by 4712

Abstract

Prostate cancer (PCa) is the second most diagnosed cancer in men worldwide. For its screening, serum prostate specific antigen (PSA) test has been largely performed over the past decade, despite its lack of accuracy and inability to distinguish indolent from aggressive disease. Metabolomics [...] Read more.

Prostate cancer (PCa) is the second most diagnosed cancer in men worldwide. For its screening, serum prostate specific antigen (PSA) test has been largely performed over the past decade, despite its lack of accuracy and inability to distinguish indolent from aggressive disease. Metabolomics has been widely applied in cancer biomarker discovery due to the well-known metabolic reprogramming characteristic of cancer cells. Most of the metabolomic studies have reported alterations in urine of PCa patients due its noninvasive collection, but the analysis of prostate tissue metabolome is an ideal approach to disclose specific modifications in PCa development. This review aims to summarize and discuss the most recent findings from tissue and urine metabolomic studies applied to PCa biomarker discovery. Eighteen metabolites were found consistently altered in PCa tissue among different studies, including alanine, arginine, uracil, glutamate, fumarate, and citrate. Urine metabolomic studies also showed consistency in the dysregulation of 15 metabolites and, interestingly, alterations in the levels of valine, taurine, leucine and citrate were found in common between urine and tissue studies. These findings unveil that the impact of PCa development in human metabolome may offer a promising strategy to find novel biomarkers for PCa diagnosis. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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10 pages, 250 KiB

Open AccessReview

Exercise May Affect Metabolism in Cancer-Related Cognitive Impairment

by Muhammad Shahid and Jayoung Kim

Metabolites 2020, 10(9), 377; https://doi.org/10.3390/metabo10090377 - 20 Sep 2020

Cited by 8 | Viewed by 3111

Abstract

Cancer-related cognitive impairment (CRCI) is a significant comorbidity for cancer patients and survivors. Physical activity (PA) has been found to be a strong gene modulator that can induce structural and functional changes in the brain. PA and exercise reduce the risk of cancer [...] Read more.

Cancer-related cognitive impairment (CRCI) is a significant comorbidity for cancer patients and survivors. Physical activity (PA) has been found to be a strong gene modulator that can induce structural and functional changes in the brain. PA and exercise reduce the risk of cancer development and progression and has been shown to help in overcoming post-treatment syndromes. Exercise plays a role in controlling cancer progression through direct effects on cancer metabolism. In this review, we highlight several priorities for improving studies on CRCI in patients and its underlying potential metabolic mechanisms. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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Other

Jump to: Research, Review

25 pages, 572 KiB

Open AccessSystematic Review

Metabolomic Profiling in Lung Cancer: A Systematic Review

by Daniela Madama, Rosana Martins, Ana S. Pires, Maria F. Botelho, Marco G. Alves, Ana M. Abrantes and Carlos R. Cordeiro

Metabolites 2021, 11(9), 630; https://doi.org/10.3390/metabo11090630 - 17 Sep 2021

Cited by 13 | Viewed by 3491

Abstract

Lung cancer continues to be a significant burden worldwide and remains the leading cause of cancer-associated mortality. Two considerable challenges posed by this disease are the diagnosis of 61% of patients in advanced stages and the reduced five-year survival rate of around 4%. [...] Read more.

Lung cancer continues to be a significant burden worldwide and remains the leading cause of cancer-associated mortality. Two considerable challenges posed by this disease are the diagnosis of 61% of patients in advanced stages and the reduced five-year survival rate of around 4%. Noninvasively collected samples are gaining significant interest as new areas of knowledge are being sought and opened up. Metabolomics is one of these growing areas. In recent years, the use of metabolomics as a resource for the study of lung cancer has been growing. We conducted a systematic review of the literature from the past 10 years in order to identify some metabolites associated with lung cancer. More than 150 metabolites have been associated with lung cancer-altered metabolism. These were detected in different biological samples by different metabolomic analytical platforms. Some of the published results have been consistent, showing the presence/alteration of specific metabolites. However, there is a clear variability due to lack of a full clinical characterization of patients or standardized patients selection. In addition, few published studies have focused on the added value of the metabolomic profile as a means of predicting treatment response for lung cancer. This review reinforces the need for consistent and systematized studies, which will help make it possible to identify metabolic biomarkers and metabolic pathways responsible for the mechanisms that promote tumor progression, relapse and eventually resistance to therapy. Full article

(This article belongs to the Special Issue Cancer Metabolomic 2020)

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