Cancer Metabolomics 2018

186 Pages·2019·12.891 MB·English

by  Paula Guedes De Pinho (editor), Márcia Carvalho (editor), Joana Pinto (editor)

Cancer
Metabolomics 2018
Edited by
Paula Guedes De Pinho, Márcia Carvalho and Joana Pinto
Printed Edition of the Special Issue Published in Metabolites
www.mdpi.com/journal/metabolites
Cancer Metabolomics 2018

Cancer Metabolomics 2018
SpecialIssueEditors
PaulaGuedesDePinho
Ma´rciaCarvalho
JoanaPinto
MDPI•Basel•Beijing•Wuhan•Barcelona•Belgrade
Special Issue Editors
Paula Guedes De Pinho Ma´rcia Carvalho
University of Porto University Fernando Pessoa
Portugal Portugal
Joana Pinto
University of Porto
Portugal
Editorial Office
MDPI
St. Alban-Anlage 66
4052 Basel, Switzerland
This is a reprint of articles from the Special Issue published online in the open access journal
Metabolites (ISSN 2218-1989) from 2018 to 2019 (available at: https://www.mdpi.com/journal/
metabolites/specialissues/cancermetabolomics2018)
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Contents
AbouttheSpecialIssueEditors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Nuria Go´mez-Cebria´n, Ayele´n Rojas-Benedicto, Arturo Albors-Vaquer, Jose´
AntonioLo´pez-Guerrero,AntonioPineda-LucenaandLeonorPuchades-Carrasco
MetabolomicsContributionstotheDiscoveryofProstateCancerBiomarkers
Reprintedfrom:Metabolites2019,9,48,doi:10.3390/metabo9030048 . . . . . . . . . . . . . . . . . 1
ShangfuLi,DanGaoandYuyangJiang
Function,DetectionandAlterationofAcylcarnitineMetabolisminHepatocellularCarcinoma
Reprintedfrom:Metabolites2019,9,36,doi:10.3390/metabo9020036 . . . . . . . . . . . . . . . . . 20
ThomasD.Horvath,WaiKinChan,MichaelA.Pontikos,LeonaA.Martin,DiDu,LinTan,
MarinaKonopleva,JohnN.WeinsteinandPhilipL.Lorenzi
AssessmentofL-AsparaginasePharmacodynamicsinMouseModelsofCancer
Reprintedfrom:Metabolites2019,9,10,doi:10.3390/metabo9010010 . . . . . . . . . . . . . . . . . 41
ZhunanJia,AbhijeetPatra,ViknishKrishnanKuttyandThirumalaiVenkatesan
CriticalReviewofVolatileOrganicCompoundAnalysisinBreathandInVitroCellCulturefor
DetectionofLungCancer
Reprintedfrom:Metabolites2019,9,52,doi:10.3390/metabo9030052 . . . . . . . . . . . . . . . . . 54
LichchaviDhananjayaRajasinghe,MelanieHutchingsandSmitiVaidGupta
Delta-Tocotrienol Modulates Glutamine Dependence by Inhibiting ASCT2 and LAT1
TransportersinNon-SmallCellLungCancer(NSCLC)Cells:AMetabolomicApproach
Reprintedfrom:Metabolites2019,9,50,doi:10.3390/metabo9030050 . . . . . . . . . . . . . . . . . 71
CatarinaSilva,RosaPerestrelo,PedroSilva,HelenaToma´sandJose´S.Caˆmara
Breast Cancer Metabolomics: From Analytical Platforms to Multivariate Data Analysis.
AReview
Reprintedfrom:Metabolites2019,9,102,doi:10.3390/metabo9050102 . . . . . . . . . . . . . . . . 92
MikheilGogiashvili,JessicaNowacki,RolandHergenro¨der,JanG.Hengstler,Jo¨rgLambert
andKarolinaEdlund
HR-MASNMRBasedQuantitativeMetabolomicsinBreastCancer
Reprintedfrom:Metabolites2019,9,19,doi:10.3390/metabo9020019 . . . . . . . . . . . . . . . . . 123
RongYou,JinDai,PingZhang,GregoryA.BardingJr.andDanielRaftery
DynamicMetabolicResponsetoAdriamycin-InducedSenescenceinBreastCancerCells
Reprintedfrom:Metabolites2018,8,95,doi:10.3390/metabo8040095 . . . . . . . . . . . . . . . . . 150
DanielaRodrigues,JoanaPinto,AnaMargaridaArau´jo,CarmenJero´nimo,RuiHenrique,
MariadeLourdesBastos,PaulaGuedesdePinhoandMa´rciaCarvalho
GC-MS Metabolomics Reveals Distinct Profiles of Low- and High-Grade Bladder Cancer
CulturedCells
Reprintedfrom:Metabolites2019,9,18,doi:10.3390/metabo9010018 . . . . . . . . . . . . . . . . . 163
v

About the Special Issue Editors
Paula Guedes de Pinho is graduated in Pharmaceutical Sciences by the Faculty of Pharmacy
of University of Porto (FFUP) and completed a PhD degree in Medical and Biological Sciences
at the University of Bordeaux II, France. During her PhD work, she specialized in biochemical
mechanismsoflivingorganisms, byusinganalyticalmethodologiessuchasChromatographyand
Mass Spectrometry. She is presently Coordinator Researcher at UCIBIO-REQUIMTE/FFUP and
Invited Associate Professor (with Habilitation) at the Faculty of Science of University of Porto
(DepartmentofBiology). Shepublishedmorethan200papers(h-index33-Scopus)ininternational
peerreviewjournals,13bookchapters,and5prizesorawards. SheisresponsibleattheLaboratory
of Toxicology of FFUP for GC-MS analysis. She implemented the research line of metabolomics
applied to cancer biomarker discovery at the Laboratory of Toxicology of FFUP, getting financed
projectsforitsdevelopment.
Ma´rciaCarvalhoisgraduatedinPharmaceuticalSciencesbytheFacultyofPharmacy, University
of Porto (FFUP), Portugal. She holds a Master in Science degree in Quality Control—Scientific
Area in Drug Substances and Medicinal Plants, and a PhD degree in Toxicology from the same
University. Ma´rciaCarvalhoispresentlyAssociateProfessorofToxicologyattheFacultyofHealth
Sciences,UniversityFernandoPessoa(Porto,Portugal),researcherattheCEBIMED/FP-ENAS(UFP,
Portugal) and at the Laboratory of Toxicology of the Associated Laboratory UCIBIO-REQUIMTE
(FFUP, Portugal). Her main areas of research are Toxicology and Metabolomics, with a special
interestinmechanisticstudiestoelucidatethetoxicityofdrugsofabuseandmetabolomicsstudies
fortheidentificationofbiomarkersandmetabolicpathwaysalteredinurologicalcancers. Shehas
publishedover70papersininternationalscientificjournals/bookchaptersinthesefields,andholds
anh-indexof27.
JoanaPintoholdsaBScdegreeinBiochemistry(2008),aMScinBiomolecularMethods(2010)anda
PhDinBiochemistry(2015)fromtheUniversityofAveiro, Portugal. HerPhDthesiswasfocused
on the investigation of potential biomarkers of several prenatal disorders through NMR-based
metabolomicanalysisofmaternalbloodplasma. Sheiscurrentlyaresearcherandco-PIinaproject
aimingthedefinitionofavolatilesignaturecharacteristicofrenalcellcarcinomabasedonGC-MS
metabolomics and electronic nose analysis, at the Associated Laboratory UCIBIO@REQUIMTE,
Faculty of Pharmacy, University of Porto, Portugal. Joana Pinto has published 1 book chapter,
22articlesininternationalpeer-reviewedjournalsand3scientificconferenceproceedings(h-index9).
HercurrentresearchinterestsarebiomarkerdiscoveryusingGC-MSandNMRbasedmetabolomics
for diagnosis, prognosis and treatment improvement and the development of new non-invasive
diagnostictoolsforcancerdetectionbasedontheprofileofurinaryvolatilecompounds.
vii

H metabolites
OH
OH
Review
Metabolomics Contributions to the Discovery of
Prostate Cancer Biomarkers
NuriaGómez-Cebrián1,2,3,AyelénRojas-Benedicto1,2,ArturoAlbors-Vaquer1,2,
JoséAntonioLópez-Guerrero3,AntonioPineda-Lucena1,2andLeonorPuchades-Carrasco2,*
1 DrugDiscoveryUnit,InstitutodeInvestigaciónSanitariaLaFe,Valencia46026,Spain;
[email protected](N.G.-C.);[email protected](A.R.-B.);[email protected](A.A.-V.);
[email protected](A.P.-L.)
2 JointResearchUnitinClinicalMetabolomics,CentrodeInvestigaciónPríncipeFelipe/Institutode
InvestigaciónSanitariaLaFe,Valencia46012,Spain
3 LaboratoryofMolecularBiology,FundaciónInstitutoValencianodeOncología,Valencia46009,Spain;
jalopez@fivo.org
* Correspondence:[email protected];Tel.:[phone]
Received:31January2019;Accepted:4March2019;Published:8March2019
Abstract:Prostatecancer(PCa)isoneofthemostfrequentlydiagnosedcancersandaleadingcause
ofdeathamongmenworldwide.Despiteextensiveeffortsinbiomarkerdiscoveryduringthelast
years,currentlyusedclinicalbiomarkersarestilllackingenoughspecificityandsensitivityforPCa
earlydetection,patientprognosis,andmonitoring.Therefore,moreprecisebiomarkersarerequired
toimprovetheclinicalmanagementofPCapatients. Inthiscontext,metabolomicshasshownto
beapromisingandpowerfultooltoidentifynovelPCabiomarkersinbiofluids. Thus,changes
inpolyamines,tricarboxylicacid(TCA)cycle,aminoacids,andfattyacidsmetabolismhavebeen
reportedindifferentstudiesanalyzingPCapatients’biofluids.Thereviewprovidesanup-to-date
summaryofthemainmetabolicalterationsthathavebeendescribedinbiofluid-basedstudiesof
PCapatients,aswellasadiscussionregardingtheirpotentialtoimproveclinicalPCadiagnosisand
prognosis.Furthermore,asummaryofthemostsignificantfindingsreportedinthesestudiesand
theconnectionsandinteractionsbetweenthedifferentmetabolicchangesdescribedhasalsobeen
included,aimingtobetterdescribethespecificmetabolicsignatureassociatedtoPCa.
Keywords:metabolomics;metabolism;prostatecancer;biomarker;earlydiagnosis;prognosis
1.Introduction
Prostate cancer (PCa) is the second most frequently diagnosed cancer and represents the
fifth leading cause of death in men [1]. In 2018, new cases of PCa were estimated to account
for over 1.3 million, and 359.000 PCa-associated deaths were expected worldwide [1]. PCa is a
hormone-dependent tumor characterized by an extremely variable clinical course, ranging from
anindolentconditiontoarapidprogressionintoanaggressivephenotypethatdisseminatesand
metastasizes to the lymph nodes and bones. Moreover, there is a current lack of reliable and
reproducibleassaystoidentifytumorsdestinedtoremainindolent.Thus,stratifyingPCapatientsinto
differentriskphenotypesattimeofdiagnosisisstillamajorclinicalchallenge.
Nowadays, PCascreeningtestsrelyonthedeterminationofprostate-specificantigen(PSA)
serum levels and digital rectal examination (DRE). Based on the results of these screening tests,
trans-rectal ultrasound (TRUS)-guided prostate biopsy is performed to confirm diagnosis when
necessary. However, thesetestssufferfromanumberoflimitationsanddonotprovideenough
informationtoenableaprecisediscriminationbetweenindolentandaggressivetumors.WhilePSA
provideshighsensitivityandlowspecificityforPCadiagnosis,(TRUS)-guidedprostatebiopsyhasbeen
Metabolites2019,9,48;doi:10.3390/metabo9030048 1 www.mdpi.com/journal/metabolites