Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker

In prostate cancer and other malignancies sensitive and robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in prostate cancer, is suffering from low specificity. Exosomes offer new perspectives in the discovery of blood-based b...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Worst, Thomas (VerfasserIn) , Hardenberg, Jost von (VerfasserIn) , Groß, Julia Christina (VerfasserIn) , Erben, Philipp (VerfasserIn) , Schnölzer, Martina (VerfasserIn) , Haußer-Siller, Ingrid (VerfasserIn) , Bugert, Peter (VerfasserIn) , Michel, Maurice Stephan (VerfasserIn) , Boutros, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: April 9, 2017
In: Molecular & cellular proteomics
Year: 2017, Jahrgang: 16, Heft: 6, Pages: 998-1008
ISSN:1535-9484
DOI:10.1074/mcp.M117.068577
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1074/mcp.M117.068577
Verlag, kostenfrei, Volltext: http://www.mcponline.org/content/16/6/998
Volltext
Verfasserangaben:Thomas Stefan Worst, Jost von Hardenberg, Julia Christina Gross, Philipp Erben, Martina Schnölzer, Ingrid Hausser, Peter Bugert, Maurice Stephan Michel and Michael Boutros

MARC

LEADER 00000caa a2200000 c 4500
001 1581894414
003 DE-627
005 20220815031322.0
007 cr uuu---uuuuu
008 181015s2017 xx |||||o 00| ||eng c
024 7 |a 10.1074/mcp.M117.068577  |2 doi 
035 |a (DE-627)1581894414 
035 |a (DE-576)511894414 
035 |a (DE-599)BSZ511894414 
035 |a (OCoLC)1341019926 
040 |a DE-627  |b ger  |c DE-627  |e rda 
041 |a eng 
084 |a 33  |2 sdnb 
100 1 |a Worst, Thomas  |d 1985-  |e VerfasserIn  |0 (DE-588)1028335679  |0 (DE-627)73058500X  |0 (DE-576)375827501  |4 aut 
245 1 0 |a Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker  |c Thomas Stefan Worst, Jost von Hardenberg, Julia Christina Gross, Philipp Erben, Martina Schnölzer, Ingrid Hausser, Peter Bugert, Maurice Stephan Michel and Michael Boutros 
264 1 |c April 9, 2017 
300 |a 11 
336 |a Text  |b txt  |2 rdacontent 
337 |a Computermedien  |b c  |2 rdamedia 
338 |a Online-Ressource  |b cr  |2 rdacarrier 
500 |a Gesehen am 15.10.2018 
520 |a In prostate cancer and other malignancies sensitive and robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in prostate cancer, is suffering from low specificity. Exosomes offer new perspectives in the discovery of blood-based biomarkers. Here we present a proof-of principle study for a proteomics-based identification pipeline, implementing existing data sources, to exemplarily identify exosome-based biomarker candidates in prostate cancer. Exosomes from malignant PC3 and benign PNT1A cells and from FBS-containing medium were isolated using sequential ultracentrifugation. Exosome and control samples were analyzed on an LTQ-Orbitrap XL mass spectrometer. Proteomic data is available via ProteomeXchange with identifier PXD003651. We developed a scoring scheme to rank 64 proteins exclusively found in PC3 exosomes, integrating data from four public databases and published mass spectrometry data sets. Among the top candidates, we focused on the tight junction protein claudin 3. Retests under serum-free conditions using immunoblotting and immunogold labeling confirmed the presence of claudin 3 on PC3 exosomes. Claudin 3 levels were determined in the blood plasma of patients with localized (n = 58; 42 with Gleason score 6-7, 16 with Gleason score ≥8) and metastatic prostate cancer (n = 11) compared with patients with benign prostatic hyperplasia (n = 15) and healthy individuals (n = 15) using ELISA, without prior laborious exosome isolation. ANOVA showed different CLDN3 plasma levels in these groups (p = 0.004). CLDN3 levels were higher in patients with Gleason ≥8 tumors compared with patients with benign prostatic hyperplasia (p = 0.012) and Gleason 6-7 tumors (p = 0.029). In patients with localized tumors CLDN3 levels predicted a Gleason score ≥ 8 (AUC = 0.705; p = 0.016) and did not correlate with serum PSA. By using the described workflow claudin 3 was identified and validated as a potential blood-based biomarker in prostate cancer. Furthermore this workflow could serve as a template to be used in other cancer entities. 
700 1 |a Hardenberg, Jost von  |d 1982-  |e VerfasserIn  |0 (DE-588)1020494328  |0 (DE-627)688149278  |0 (DE-576)360578241  |4 aut 
700 1 |a Groß, Julia Christina  |d 1980-  |e VerfasserIn  |0 (DE-588)139632840  |0 (DE-627)703407155  |0 (DE-576)31252224X  |4 aut 
700 1 |a Erben, Philipp  |d 1973-  |e VerfasserIn  |0 (DE-588)128501014  |0 (DE-627)373920997  |0 (DE-576)297181661  |4 aut 
700 1 |a Schnölzer, Martina  |e VerfasserIn  |0 (DE-588)1158026110  |0 (DE-627)1021753610  |0 (DE-576)503538213  |4 aut 
700 1 |a Haußer-Siller, Ingrid  |d 1957-  |e VerfasserIn  |0 (DE-588)1058096710  |0 (DE-627)796384703  |0 (DE-576)163782377  |4 aut 
700 1 |a Bugert, Peter  |d 1964-  |e VerfasserIn  |0 (DE-588)1025332342  |0 (DE-627)722074018  |0 (DE-576)370212169  |4 aut 
700 1 |a Michel, Maurice Stephan  |d 1970-  |e VerfasserIn  |0 (DE-588)121842568  |0 (DE-627)705674134  |0 (DE-576)29291363X  |4 aut 
700 1 |a Boutros, Michael  |e VerfasserIn  |0 (DE-588)1023031132  |0 (DE-627)717350045  |0 (DE-576)366291831  |4 aut 
773 0 8 |i Enthalten in  |t Molecular & cellular proteomics  |d Bethesda, Md. : The American Society for Biochemistry and Molecular Biology, 2002  |g 16(2017), 6, Seite 998-1008  |h Online-Ressource  |w (DE-627)342318276  |w (DE-600)2071375-7  |w (DE-576)264424549  |x 1535-9484  |7 nnas  |a Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker 
773 1 8 |g volume:16  |g year:2017  |g number:6  |g pages:998-1008  |g extent:11  |a Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker 
856 4 0 |u http://dx.doi.org/10.1074/mcp.M117.068577  |x Verlag  |x Resolving-System  |z kostenfrei  |3 Volltext 
856 4 0 |u http://www.mcponline.org/content/16/6/998  |x Verlag  |z kostenfrei  |3 Volltext 
951 |a AR 
992 |a 20181015 
993 |a Article 
994 |a 2017 
998 |g 1023031132  |a Boutros, Michael  |m 1023031132:Boutros, Michael  |d 60000  |e 60000PB1023031132  |k 0/60000/  |p 9 
998 |g 121842568  |a Michel, Maurice Stephan  |m 121842568:Michel, Maurice Stephan  |d 60000  |d 63100  |e 60000PM121842568  |e 63100PM121842568  |k 0/60000/  |k 1/60000/63100/  |p 8 
998 |g 1025332342  |a Bugert, Peter  |m 1025332342:Bugert, Peter  |d 60000  |d 63500  |e 60000PB1025332342  |e 63500PB1025332342  |k 0/60000/  |k 1/60000/63500/  |p 7 
998 |g 1058096710  |a Haußer-Siller, Ingrid  |m 1058096710:Haußer-Siller, Ingrid  |d 910000  |d 912000  |e 910000PH1058096710  |e 912000PH1058096710  |k 0/910000/  |k 1/910000/912000/  |p 6 
998 |g 1158026110  |a Schnölzer, Martina  |m 1158026110:Schnölzer, Martina  |d 140000  |e 140000PS1158026110  |k 0/140000/  |p 5 
998 |g 128501014  |a Erben, Philipp  |m 128501014:Erben, Philipp  |d 60000  |d 63100  |e 60000PE128501014  |e 63100PE128501014  |k 0/60000/  |k 1/60000/63100/  |p 4 
998 |g 139632840  |a Groß, Julia Christina  |m 139632840:Groß, Julia Christina  |d 60000  |d 999810  |e 60000PG139632840  |e 999810PG139632840  |k 0/60000/  |k 1/60000/999810/  |p 3 
998 |g 1020494328  |a Hardenberg, Jost von  |m 1020494328:Hardenberg, Jost von  |d 60000  |d 63100  |e 60000PH1020494328  |e 63100PH1020494328  |k 0/60000/  |k 1/60000/63100/  |p 2 
998 |g 1028335679  |a Worst, Thomas  |m 1028335679:Worst, Thomas  |d 60000  |d 63100  |e 60000PW1028335679  |e 63100PW1028335679  |k 0/60000/  |k 1/60000/63100/  |p 1  |x j 
999 |a KXP-PPN1581894414  |e 3028733730 
BIB |a Y 
SER |a journal 
JSO |a {"physDesc":[{"extent":"11 S."}],"recId":"1581894414","origin":[{"dateIssuedKey":"2017","dateIssuedDisp":"April 9, 2017"}],"person":[{"display":"Worst, Thomas","family":"Worst","given":"Thomas","role":"aut"},{"display":"Hardenberg, Jost von","role":"aut","given":"Jost von","family":"Hardenberg"},{"display":"Groß, Julia Christina","family":"Groß","given":"Julia Christina","role":"aut"},{"role":"aut","given":"Philipp","family":"Erben","display":"Erben, Philipp"},{"role":"aut","given":"Martina","family":"Schnölzer","display":"Schnölzer, Martina"},{"family":"Haußer-Siller","given":"Ingrid","role":"aut","display":"Haußer-Siller, Ingrid"},{"family":"Bugert","given":"Peter","role":"aut","display":"Bugert, Peter"},{"display":"Michel, Maurice Stephan","given":"Maurice Stephan","role":"aut","family":"Michel"},{"display":"Boutros, Michael","family":"Boutros","role":"aut","given":"Michael"}],"relHost":[{"id":{"zdb":["2071375-7"],"eki":["342318276"],"issn":["1535-9484"]},"part":{"pages":"998-1008","issue":"6","text":"16(2017), 6, Seite 998-1008","extent":"11","year":"2017","volume":"16"},"name":{"displayForm":["The American Society for Biochemistry and Molecular Biology (ASBMB)"]},"pubHistory":["1.2002 -"],"titleAlt":[{"title":"MCP"},{"title":"Molecular and cellular proteomics"}],"language":["eng"],"type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 23.05.25"],"title":[{"title_sort":"Molecular & cellular proteomics","title":"Molecular & cellular proteomics","subtitle":"MCP"}],"origin":[{"publisherPlace":"Bethesda, Md.","dateIssuedKey":"2002","dateIssuedDisp":"2002-","publisher":"The American Society for Biochemistry and Molecular Biology"}],"disp":"Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarkerMolecular & cellular proteomics","physDesc":[{"extent":"Online-Ressource"}],"recId":"342318276"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"note":["Gesehen am 15.10.2018"],"title":[{"title":"Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker","title_sort":"Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker"}],"name":{"displayForm":["Thomas Stefan Worst, Jost von Hardenberg, Julia Christina Gross, Philipp Erben, Martina Schnölzer, Ingrid Hausser, Peter Bugert, Maurice Stephan Michel and Michael Boutros"]},"id":{"eki":["1581894414"],"doi":["10.1074/mcp.M117.068577"]}} 
SRT |a WORSTTHOMADATABASEAU9201