Le SOMAscan, une approche innovante pour le dosage simultané de 1 305 protéines : application à l’étude du cancer et des maladies cardio-vasculaires

Genopole - Séminaire "Sciences & Techno" - Biomarqueurs et Protéomique
Le#SOMAscan,#une#approche#innovante#pour#le#dosage#simultané#de#1#305#protéines#:#
application#à#l’étude#du#cancer#et#des#maladies#cardio-vasculaires#
Jeudi&27/04/2017&au&LAMBE&(UEVE)&
#
#
10h00-10h30#:#Use#of#modified#aptamers#as#a#new#proteomics#tool#for#unprecedented#
multiplex#assay#-#the#SOMAscan#
Nicolas#Autret,#PhD#–#SomaLogic#–#[email protected]#
Even&though&proteins&are&the&targets&of&95%&of&all&known&drugs,&and&downstream&of&both&
genetics& and& the& environment,& proteomics& has& failed& to& generate& even& a& fraction& of& the&
excitement& that& drives& the& genomics& revolution.& This& has& been& justifiable& until& now& because&
large&scale,&high&throughput,&highly&multiplexed&protein&measurements&have&not&been&possible.&&&
With& the& availability& of& the& SOMAscan& 1.3k& assay,& using& modified& DNA-based& reagents& which& form& highly& specific&
complexes& with& proteins,& we& have& re-purposed& genetic& technologies& to& measure& proteins& at& unprecedented& scale& and&
performance:&sub-picogram&detection&of&thousands&of&proteins&with&high&precision&and&tiny&volumes&of&sample.&
Examples& from& cancer,& neurological& disorders&up& to& cardiovascular& diseases& will& be& shown& of& how& the& individual& novel&
reagents& as& well& as& the& SOMAscan& assay& are& being& used& to& uncover& new& biology,& validate& new& targets,& compliment&
genomics&findings&and&deliver&actionable&information&for&medical&practice&and&drug&development.&
10h40-11h10#-# Predictive# biomarkers# for# the# response# to# treatments# in# triple-negative# breast# cancer:# use# of# the#
SOMAscan#in#addition#to#the#reverse-phase#protein#array#(RPPA)#technology.#
Leanne#de#Koning,#PhD#–#Institut#Curie#–#leanne.de-[email protected]#
Triple&negative&breast&cancer&(TNBC),&characterized&by&the&absence&of&hormone&receptors&and&no&HER2&overexpression,&is&
a&heterogeneous&group&of&breast&cancers&with&bad&prognosis&due&to&early&relapse.&No&targeted&therapy&options&currently&
exist.&Here,& we&wanted&to&establish&the&tumor&protein&profile&of&our&triple&negative&cell&models&grown&in&2D&and&3D,&in&
order&to&(i)&refine&the&classification&of&this&very&heterogeneous&subgroup,&(ii)&identify&predictive&biomarkers&or&signatures&
to&better&adapt&treatments,&and&(iii)&to&propose&new&therapeutic&strategies&via&the&discovery&of&target&proteins.&&
Somascan&technology&has&allowed&us&to&probe&1305&different&proteins&in&a&wide&screen&and&thus&point&out&the&signaling&
pathways&that&can&be&deregulated&in&the&triple&negative&cell&lines&grown&in&3D.&The&results&are&then&validated&and&further&
developed&with&the&Reverse&Phase&Protein&Array&(RPPA)&technology,&which&allows&not&only&to&quantify&the&total&amount&of&
protein&but&also&their&post-translational&modifications&such&as&phosphorylation&to&be&studied.&&
Unlike&Somascan,&RPPA&requires&a&precise&selection&of&the&proteins&to&be&analyzed,&but&it&allows&to&study&550&samples&on&a&
single&chip.&The&two&technologies&are&thus&complementary:&the&Somascan&allows&us&to&select&from&about&thirty&samples&
the&proteins&and&signaling&pathways&of&interest&which&are&then&studied&more&finely&in&RPPA&on&a&large&series&of&samples,&
including&not&only&cell&lines&but&also&xenografts&and&patient&tumors.&
11h20-11h50#:#Interest#of# multi-marker#approach#for#predicting#early#mortality#in#heart#failure#patients#with#reduced#
ejection#fraction#
Florence#Pinet,#M.D.,#PhD#–#Institut#Pasteur#de#Lille#–#[e-mail]#
Our&objective&is&to&find&new&biomarkers&associated&with&early&cardiovascular&mortality&in&heart&failure&by&a&multi-marker&
approach.& For& that& purpose& we& used& a& prospective& register& (INCA& study)& including& consecutively& heart& failure& patients&
(systolic&HF&with&LVEF&≤&45%),&clinically&stable&(no&decompensation,&no&hospitalization&in&the&previous&2&months)&with&an&
optimal&medical&therapy.&&
The& patients& undergo& a& prognostic& evaluation& (NYHA& class,& BNP& levels,& LVEF& measurement,& Peak& VO2&obtained& during&
cardiopulmonary&exercise&testing).&All&patients&had&a&coronarography&for&determining&etiology&of&cardiopathy.&&
We&compare&protein&signals&in&plasma&from&INCA&study&heart&failure&participants&who&were&alive&(n=84)&or&dead&(n=84)&
within&3&years&after&study&enrollment&with&SOMAscan&1.3k&assay,&measuring&1,305&proteins.&4&samples&(all&controls)&failed&
SOMAscan&QC&criteria&and&were&excluded&from&the&analysis.&We&found&a&correlation&between&the&levels&of&BNP&quantified&
by&BNP&SOMAmer&with&Clinical&BNP.&345&proteins&and&2&clinical&variables&were&significant&at&KS&test&FDR&p<0.05.&&
The&next&step&is&an&integrative&analysis&of&molecular&and& clinical&data&in&order&to&build&a&molecular&interaction&network&
under&cytoscape.&