Bioinformatics Tools and Workflow to Select Blood Biomarkers for Early Cancer Diagnosis: An Application to Pancreatic Cancer

Vandenbrouck, Yves; Christiany, David; Combes, Florence; Loux, Valentin; Brun, Virginie

doi:10.1002/pmic.201800489

“…However, newer technologies such as proteomics allow large-scale analyses of proteins, including relative abundance and functional inter-relationships, on the same samples. 24–28 Although proteomics approaches have been applied to the field of neuroscience, 29–30 to date there are no reported studies of sex-dependent differences in mitochondria-related proteins in brain MVs.…”

Section: Introductionmentioning

confidence: 99%

Sexual differences in mitochondrial and related proteins in rat cerebral microvessels: A proteomic approach

Čikić

¹

,

Chandra

²

,

Harman

³

et al. 2020

J Cereb Blood Flow Metab

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Sex differences in mitochondrial numbers and function are present in large cerebral arteries, but it is unclear whether these differences extend to the microcirculation. We performed an assessment of mitochondria-related proteins in cerebral microvessels (MVs) isolated from young, male and female, Sprague-Dawley rats. MVs composed of arterioles, capillaries, and venules were isolated from the cerebrum and used to perform a 3 versus 3 quantitative, multiplexed proteomics experiment utilizing tandem mass tags (TMT), coupled with liquid chromatography/mass spectrometry (LC/MS). MS data and bioinformatic analyses were performed using Proteome Discoverer version 2.2 and Ingenuity Pathway Analysis. We identified a total of 1969 proteins, of which 1871 were quantified by TMT labels. Sixty-four proteins were expressed significantly ( p < 0.05) higher in female samples compared with male samples. Females expressed more mitochondrial proteins involved in energy production, mitochondrial membrane structure, anti-oxidant enzyme proteins, and those involved in fatty acid oxidation. Conversely, males had higher expression levels of mitochondria-destructive proteins. Our findings reveal, for the first time, the full extent of sexual dimorphism in the mitochondrial metabolic protein profiles of MVs, which may contribute to sex-dependent cerebrovascular and neurological pathologies.

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“…Blood circulating biomarkers for detecting early pancreatic cancers have been discovered including circulating tumor DNA [111,112], exome-derived DNA [113], MicroRNA [114] (miR-93, miR-16, miR-548d-3p, etc. ), and proteins [115] (SYCN, REG1B, PRSS2, etc.). Liu et al [112].…”

Section: Application Of Blood Circulating Biomarkers For Detecting Eamentioning

confidence: 99%

Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers

Matsubayashi

¹

,

Kiyozumi

²

,

Ishiwatari

³

et al. 2019

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A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz–Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%–10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection.

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“…Traditional methodologies, such as Western blotting, restrict the number of mitochondrial-related proteins in cerebral blood vessels that could be efficiently studied at one time and require a priori 5 decisions concerning protein selection. However, newer technologies such as proteomics allow largescale analyses of proteins, including relative abundance and functional inter-relationships, on the same samples (Brzica et al, 2018;Harman et al, 2018;Javitt & Marbl 2019;Tharakan et al, 2019;Vandenbrouck et al, 2019). Although proteomics approaches have been applied to the field of neuroscience (Gomez-Zepeda et al, 2019;Porte et al, 2017), to date there are no reported studies of sexdependent differences in mitochondria-related proteins in brain MVs.…”

Section: Introductionmentioning

confidence: 99%

Sexual Differences in Mitochondrial Proteins in Rat Cerebral Microvessels: A Proteomic Approach

Chandra

¹

,

Čikić

²

,

Harman

³

et al. 2019

Preprint

1

0

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Sex differences in mitochondrial numbers and function are present in large cerebral arteries, but it is unclear whether these differences extend to the microcirculation. We performed an assessment of mitochondria-related proteins in cerebral microvessels (MVs) isolated from young, male and female, Sprague-Dawley rats. MVs composed of arterioles, capillaries, and venules were isolated from the cerebrum and used to perform a 3 vs. 3 quantitative, multiplexed proteomics experiment utilizing tandem mass tags (TMT), coupled with liquid chromatography/mass spectrometry (LC/MS). MS data and bioinformatic analyses were performed using Proteome Discoverer version 2.2 and Ingenuity Pathway Analysis. We identified a total of 1,969 proteins, of which 1,871 were quantified by TMT labels. Sixty-four proteins were expressed significantly (p < 0.05) higher in female samples compared with male samples. Females expressed more mitochondrial proteins involved in energy production, mitochondrial membrane structure, anti-oxidant enzyme proteins, and those involved in fatty acid oxidation. Conversely, males had higher expression levels of mitochondria-destructive proteins. We validated our key Proteomics results with western blotting. Our findings reveal, for the first time, the full extent of sexual dimorphism in the mitochondrial metabolic protein profiles of MVs, which may contribute to sex-dependent cerebrovascular and neurological pathologies. SynopsisEnergy-producing proteins in the cerebral microvessels (MVs) of male and female rats were examined by quantitative discovery-based proteomics to gain insight into the sex-dependent etiology of cardiovascular and neurological diseases. Females expressed more mitochondrial proteins involved in energy production, membrane structure, anti-oxidant activity, and fatty acid oxidation. In contrast, males exhibited more mitochondria-destructive proteins such as mitochondrial eating protein. Our findings reveal for the first time the sexual dimorphism of mitochondria-related proteins in cerebral MVs, which may explain functional sex-related differences in MVs during health and in the etiology of neurological pathologies of cerebrovascular origin. ACKNOWLEDGMENTSWe thank Nancy Busija, MA, for editing the manuscript. We thank Dana Liu for technical help.

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Bioinformatics Tools and Workflow to Select Blood Biomarkers for Early Cancer Diagnosis: An Application to Pancreatic Cancer

Cited by 26 publications

References 37 publications

Sexual differences in mitochondrial and related proteins in rat cerebral microvessels: A proteomic approach

Sexual differences in mitochondrial and related proteins in rat cerebral microvessels: A proteomic approach

Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers

Sexual Differences in Mitochondrial Proteins in Rat Cerebral Microvessels: A Proteomic Approach

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