PittsburghV1, Canada, Analysis, bibRecord, 000330

Blood mRNA Expression Profiling Predicts Survival in Patients Treated with Tremelimumab

Identifieur interne : 000330 ( Canada/Analysis ); précédent : 000329; suivant : 000331

Blood mRNA Expression Profiling Predicts Survival in Patients Treated with Tremelimumab

Auteurs : Yvonne Saenger [États-Unis] ; Jay Magidson [États-Unis] ; Bobby Liaw [États-Unis] ; Ellen De Moll [États-Unis] ; Sara Harcharik [États-Unis] ; YICHUN FU [États-Unis] ; Karl Wassmann [Canada] ; David Fisher [États-Unis] ; John Kirkwood [États-Unis] ; William K. Oh [États-Unis] ; Philip Friedlander [États-Unis]

Source :

Clinical cancer research : (Print) [ 1078-0432 ] ; 2014.

RBID : Pascal:14-0167493

Descripteurs français

KwdFr :
- ARN messager (génétique), ARN messager (sang), Adolescent, Adulte, Adulte d'âge moyen, Analyse de profil d'expression de gènes, Anticorps monoclonaux (usage thérapeutique), Antinéoplasiques (usage thérapeutique), Femelle, Humains, Jeune adulte, Marqueurs biologiques tumoraux (génétique), Marqueurs biologiques tumoraux (sang), Mâle, Mélanome (génétique), Mélanome (mortalité), Mélanome (traitement médicamenteux), Pronostic, RT-PCR, Réaction de polymérisation en chaine en temps réel, Résistance aux médicaments antinéoplasiques (génétique), Stade de la tumeur, Sujet âgé, Sujet âgé de 80 ans ou plus, Séquençage par oligonucléotides en batterie, Taux de survie, Études prospectives.
MESH :
- génétique : ARN messager, Marqueurs biologiques tumoraux, Mélanome, Résistance aux médicaments antinéoplasiques.
- mortalité : Mélanome.
- sang : ARN messager, Marqueurs biologiques tumoraux.
- traitement médicamenteux : Mélanome.
- usage thérapeutique : Anticorps monoclonaux, Antinéoplasiques.
Pascal (Inist)
- Adolescent, Adulte, Adulte d'âge moyen, Analyse de profil d'expression de gènes, Femelle, Humains, Jeune adulte, Liquide biologique, Mâle, Pronostic, RT-PCR, Réaction de polymérisation en chaine en temps réel, Sang, RNA messager, Facteur prédictif, Stade de la tumeur, Sujet âgé, Sujet âgé de 80 ans ou plus, Survie, Homme, Séquençage par oligonucléotides en batterie, Taux de survie, Traitement, Trémélimumab, Profil d'expression génique, Études prospectives.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal (therapeutic use), Antineoplastic Agents (therapeutic use), Biological fluid, Biomarkers, Tumor (blood), Biomarkers, Tumor (genetics), Blood, Drug Resistance, Neoplasm (genetics), Female, Gene Expression Profiling, Gene expression profile, Human, Humans, Male, Melanoma (drug therapy), Melanoma (genetics), Melanoma (mortality), Messenger RNA, Middle Aged, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Predictive factor, Prognosis, Prospective Studies, RNA, Messenger (blood), RNA, Messenger (genetics), Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Survival, Survival Rate, Treatment, Tremelimumab, Young Adult.
MESH :
- chemical , blood : Biomarkers, Tumor, RNA, Messenger.
- chemical , genetics : Biomarkers, Tumor, RNA, Messenger.
- chemical , therapeutic use : Antibodies, Monoclonal, Antineoplastic Agents.
- drug therapy : Melanoma.
- genetics : Drug Resistance, Neoplasm, Melanoma.
- mortality : Melanoma.
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Gene Expression Profiling, Humans, Male, Middle Aged, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Prognosis, Prospective Studies, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Young Adult.

Abstract

Purpose: Tremelimumab (ticilimumab, Pfizer), is a monoclonal antibody (mAb) targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Ipilimumab (Yervoy, BMS), another anti-CTLA-4 antibody, is approved by the U.S. Federal Drug Administration (FDA). Biomarkers are needed to identify the subset of patients who will achieve tumor control with CTLA-4 blockade. Experimental Design: Pretreatment peripheral blood samples from 218 patients with melanoma who were refractory to prior therapy and receiving tremelimumab in a multicenter phase II study were measured for 169 mRNA transcripts using reverse transcription polymerase chain reaction (RT-PCR). A two-class latent model yielded a risk score based on four genes that were highly predictive of survival (P < 0.001). This signature was validated in an independent population of 260 treatment-naive patients with melanoma enrolled in a multicenter phase III study of tremelimumab. Results: Median follow-up was 297 days for the training population and 386 days for the test population. Expression levels of the 169 genes were closely correlated across the two populations (r = 0.9939). A four-gene model, including cathepsin D (CTSD), phopholipase A2 group VII (PLA2G7), thioredoxin reductase 1 (TXNRD1), and interleukin 1 receptor-associated kinase 3 (IRAK3), predicted survival in the test population (P = 0.001 by log-rank test). This four-gene model added to the predictive value of clinical predictors (P < 0.0001). Conclusions: Expression levels of CTSD, PLA2G7, TXNRD1, and IRAK3 in peripheral blood are predictive of survival in patients with melanoma treated with tremelimumab. Blood mRNA signatures should be further explored to define patient subsets likely to benefit from immunotherapy.

Affiliations:

Links to Exploration step

Pascal:14-0167493

Le document en format XML

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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Antibodies, Monoclonal (therapeutic use)</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Biological fluid</term>
<term>Biomarkers, Tumor (blood)</term>
<term>Biomarkers, Tumor (genetics)</term>
<term>Blood</term>
<term>Drug Resistance, Neoplasm (genetics)</term>
<term>Female</term>
<term>Gene Expression Profiling</term>
<term>Gene expression profile</term>
<term>Human</term>
<term>Humans</term>
<term>Male</term>
<term>Melanoma (drug therapy)</term>
<term>Melanoma (genetics)</term>
<term>Melanoma (mortality)</term>
<term>Messenger RNA</term>
<term>Middle Aged</term>
<term>Neoplasm Staging</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Predictive factor</term>
<term>Prognosis</term>
<term>Prospective Studies</term>
<term>RNA, Messenger (blood)</term>
<term>RNA, Messenger (genetics)</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>Survival</term>
<term>Survival Rate</term>
<term>Treatment</term>
<term>Tremelimumab</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term>
<term>ARN messager (sang)</term>
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Anticorps monoclonaux (usage thérapeutique)</term>
<term>Antinéoplasiques (usage thérapeutique)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Marqueurs biologiques tumoraux (génétique)</term>
<term>Marqueurs biologiques tumoraux (sang)</term>
<term>Mâle</term>
<term>Mélanome (génétique)</term>
<term>Mélanome (mortalité)</term>
<term>Mélanome (traitement médicamenteux)</term>
<term>Pronostic</term>
<term>RT-PCR</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Résistance aux médicaments antinéoplasiques (génétique)</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Taux de survie</term>
<term>Études prospectives</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Biomarkers, Tumor</term>
<term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Biomarkers, Tumor</term>
<term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Antineoplastic Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Drug Resistance, Neoplasm</term>
<term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term>
<term>Marqueurs biologiques tumoraux</term>
<term>Mélanome</term>
<term>Résistance aux médicaments antinéoplasiques</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Mélanome</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>ARN messager</term>
<term>Marqueurs biologiques tumoraux</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Mélanome</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux</term>
<term>Antinéoplasiques</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Female</term>
<term>Gene Expression Profiling</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neoplasm Staging</term>
<term>Oligonucleotide Array Sequence Analysis</term>
<term>Prognosis</term>
<term>Prospective Studies</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>Survival Rate</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Liquide biologique</term>
<term>Mâle</term>
<term>Pronostic</term>
<term>RT-PCR</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Sang</term>
<term>RNA messager</term>
<term>Facteur prédictif</term>
<term>Stade de la tumeur</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Survie</term>
<term>Homme</term>
<term>Séquençage par oligonucléotides en batterie</term>
<term>Taux de survie</term>
<term>Traitement</term>
<term>Trémélimumab</term>
<term>Profil d'expression génique</term>
<term>Études prospectives</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Purpose: Tremelimumab (ticilimumab, Pfizer), is a monoclonal antibody (mAb) targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Ipilimumab (Yervoy, BMS), another anti-CTLA-4 antibody, is approved by the U.S. Federal Drug Administration (FDA). Biomarkers are needed to identify the subset of patients who will achieve tumor control with CTLA-4 blockade. Experimental Design: Pretreatment peripheral blood samples from 218 patients with melanoma who were refractory to prior therapy and receiving tremelimumab in a multicenter phase II study were measured for 169 mRNA transcripts using reverse transcription polymerase chain reaction (RT-PCR). A two-class latent model yielded a risk score based on four genes that were highly predictive of survival (P < 0.001). This signature was validated in an independent population of 260 treatment-naive patients with melanoma enrolled in a multicenter phase III study of tremelimumab. Results: Median follow-up was 297 days for the training population and 386 days for the test population. Expression levels of the 169 genes were closely correlated across the two populations (r = 0.9939). A four-gene model, including cathepsin D (CTSD), phopholipase A2 group VII (PLA2G7), thioredoxin reductase 1 (TXNRD1), and interleukin 1 receptor-associated kinase 3 (IRAK3), predicted survival in the test population (P = 0.001 by log-rank test). This four-gene model added to the predictive value of clinical predictors (P < 0.0001). Conclusions: Expression levels of CTSD, PLA2G7, TXNRD1, and IRAK3 in peripheral blood are predictive of survival in patients with melanoma treated with tremelimumab. Blood mRNA signatures should be further explored to define patient subsets likely to benefit from immunotherapy.</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
<li>Pennsylvanie</li>
<li>État de New York</li>
</region>
</list>
<tree><country name="États-Unis"><region name="État de New York"><name sortKey="Saenger, Yvonne" sort="Saenger, Yvonne" uniqKey="Saenger Y" first="Yvonne" last="Saenger">Yvonne Saenger</name>
</region>
<name sortKey="De Moll, Ellen" sort="De Moll, Ellen" uniqKey="De Moll E" first="Ellen" last="De Moll">Ellen De Moll</name>
<name sortKey="Fisher, David" sort="Fisher, David" uniqKey="Fisher D" first="David" last="Fisher">David Fisher</name>
<name sortKey="Friedlander, Philip" sort="Friedlander, Philip" uniqKey="Friedlander P" first="Philip" last="Friedlander">Philip Friedlander</name>
<name sortKey="Friedlander, Philip" sort="Friedlander, Philip" uniqKey="Friedlander P" first="Philip" last="Friedlander">Philip Friedlander</name>
<name sortKey="Harcharik, Sara" sort="Harcharik, Sara" uniqKey="Harcharik S" first="Sara" last="Harcharik">Sara Harcharik</name>
<name sortKey="Kirkwood, John" sort="Kirkwood, John" uniqKey="Kirkwood J" first="John" last="Kirkwood">John Kirkwood</name>
<name sortKey="Liaw, Bobby" sort="Liaw, Bobby" uniqKey="Liaw B" first="Bobby" last="Liaw">Bobby Liaw</name>
<name sortKey="Magidson, Jay" sort="Magidson, Jay" uniqKey="Magidson J" first="Jay" last="Magidson">Jay Magidson</name>
<name sortKey="Oh, William K" sort="Oh, William K" uniqKey="Oh W" first="William K." last="Oh">William K. Oh</name>
<name sortKey="Saenger, Yvonne" sort="Saenger, Yvonne" uniqKey="Saenger Y" first="Yvonne" last="Saenger">Yvonne Saenger</name>
<name sortKey="Yichun Fu" sort="Yichun Fu" uniqKey="Yichun Fu" last="Yichun Fu">YICHUN FU</name>
</country>
<country name="Canada"><noRegion><name sortKey="Wassmann, Karl" sort="Wassmann, Karl" uniqKey="Wassmann K" first="Karl" last="Wassmann">Karl Wassmann</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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   |texte=   Blood mRNA Expression Profiling Predicts Survival in Patients Treated with Tremelimumab
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Blood mRNA Expression Profiling Predicts Survival in Patients Treated with Tremelimumab

Blood mRNA Expression Profiling Predicts Survival in Patients Treated with Tremelimumab

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