Metabolomic Biomarkers for Detection, Prognosis and Identifying Recurrence in Endometrial Cancer

Njoku, Kelechi; Sutton, Caroline J. J.; Whetton, Anthony D.; Crosbie, Emma J.

doi:10.3390/metabo10080314

Cited by 39 publications

(47 citation statements)

References 114 publications

(262 reference statements)

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“…Metabolic profiling can either be targeted or untargeted. While targeted approaches deal with the measurement of a pre-defined select group of metabolites, untargeted approaches aim to comprehensively analyze all measurable products in a given sample with no prior assumptions (42,66,67). The hypothesis driven nature of targeted studies lends to a high level of precision and accuracy, in contrast to untargeted approaches which are prone to false positives (42).…”

Section: Endogenous Urinary Metabolitesmentioning

confidence: 99%

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

et al. 2020

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Endometrial cancer is the most common malignancy of the female genital tract and its incidence is rising in parallel with the mounting prevalence of obesity. Early diagnosis has great potential to improve outcomes as treatment can be curative, especially for early stage disease. Current tests and procedures for diagnosis are limited by insufficient accuracy in some and unacceptable levels of invasiveness and discomfort in others. There has, therefore, been a growing interest in the search for sensitive and specific biomarkers for endometrial cancer detection based on non-invasive sampling methodologies. Urine, the prototype non-invasive sample, is attractive for biomarker discovery as it is easily accessible and can be collected repeatedly and in quantity. Identification of urinary biomarkers for endometrial cancer detection relies on the excretion of systemic biomarkers by the kidneys or urinary contamination by biomarkers shed from the uterus. In this review, we present the current standing of the search for endometrial cancer urinary biomarkers based on cytology, genomic, transcriptomic, proteomic, and metabolomic platforms. We summarize the biomarker candidates and highlight the challenges inherent in urinary biomarker discovery. We review the various technologies with promise for biomarker detection and assess these novel approaches for endometrial cancer biomarker research.

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Section: Endogenous Urinary Metabolitesmentioning

confidence: 99%

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

et al. 2020

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“…The rising prevalence of endometrial cancer has stimulated an interest in biomarker discovery alongside minimally invasive sampling technologies for its early detection [ 11 ]. Many studies have explored the possibility of detecting endometrial cancer in blood using genetic biomarkers (including tumour DNA [ 26 ], epigenetic modifications [ 27 ] and transcripts [ 28 , 29 ]), proteins [ 18 , 30 ] and metabolites [ 19 , 22 ] through genomic, epigenomic, transcriptomic, proteomic, spectroscopic and metabolomic approaches. The metabolome reflects the functional human phenotype and as such, has enormous potential to deliver clinically relevant biomarkers for endometrial cancer detection [ 20 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…The upregulation of phospholipid biosynthetic pathways in cancer cells is a direct consequence of accelerated growth and enhanced membrane biosynthesis that accompanies tumorigenesis [ 44 ]. A recent systematic review by our group identified choline derivatives, specifically glycerophosphocholines and phosphocholines, as promising biomarkers for endometrial cancer detection [ 22 ]. Altered choline metabolism is a hallmark of carcinogenesis and is linked to mitogenic signal transduction, the regulatory mechanism that modulates cell proliferation, differentiation, metabolism and death [ 34 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Metabolomics studies the downstream products of genomic, transcriptomic, and proteomic processes and best mirrors the human phenotype [ 20 , 21 ]. Thus, metabolomics has great potential to deliver clinically relevant biomarkers for endometrial cancer detection [ 22 ]. A blood-based test for cancer has broad appeal, being rated the second most important research priority for detecting cancer early in our recent James Lind Alliance Priority Setting Partnership [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

Njoku

Campbell

Geary

et al. 2021

Cancers

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Endometrial cancer is the most common malignancy of the female genital tract and a major cause of morbidity and mortality in women. Early detection is key to ensuring good outcomes but a lack of minimally invasive screening tools is a significant barrier. Most endometrial cancers are obesity-driven and develop in the context of severe metabolomic dysfunction. Blood-derived metabolites may therefore provide clinically relevant biomarkers for endometrial cancer detection. In this study, we analysed plasma samples of women with body mass index (BMI) ≥30kg/m2 and endometrioid endometrial cancer (cases, n = 67) or histologically normal endometrium (controls, n = 69), using a mass spectrometry-based metabolomics approach. Eighty percent of the samples were randomly selected to serve as a training set and the remaining 20% were used to qualify test performance. Robust predictive models (AUC > 0.9) for endometrial cancer detection based on artificial intelligence algorithms were developed and validated. Phospholipids were of significance as biomarkers of endometrial cancer, with sphingolipids (sphingomyelins) discriminatory in post-menopausal women. An algorithm combining the top ten performing metabolites showed 92.6% prediction accuracy (AUC of 0.95) for endometrial cancer detection. These results suggest that a simple blood test could enable the early detection of endometrial cancer and provide the basis for a minimally invasive screening tool for women with a BMI ≥ 30 kg/m2.

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“…Like other cancer entities [11,12] CRC undergoes specific metabolic reprogramming during carcinogenesis [13] including dysregulation of energy [13] and lipid metabolism [14,15]. Therefore, metabolism has been suggested as a targetable vulnerability in CRC [16].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

et al. 2020

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As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) facing the challenge of capturing metabolic information from a minimal sample amount (<500 cells/injection) in the presence of an extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on the p-value and fold change cut-offs, which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2′-deoxyuridine, 2′-O-methylcytidine, inosine and 1-methyladenosine and depletion of 2′-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.

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Metabolomic Biomarkers for Detection, Prognosis and Identifying Recurrence in Endometrial Cancer

Cited by 39 publications

References 114 publications

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

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