0e363171e630aa82d5822d3a9cc8ac01 pmc_31842290.pdf b1fd8c90c8fa0f5ef5701a6e7b70282969357c2e pmc_31842290.pdf 0d40d2b6db7a3215dcdfb8978338ca1adc6f22134cfbaf21c57dc4fc8303fd59 pmc_31842290.pdf Title: Extracellular Vesicles-Based Biomarkers Represent a Promising Liquid Biopsy in Endometrial Cancer Subject: Tumor-derived extracellular vesicles (EVs) are secreted in large amounts into biological fluids of cancer patients. The analysis of EVs cargoes has been associated with patient´s outcome and response to therapy. However, current technologies for EVs isolation are tedious and low cost-efficient for routine clinical implementation. To explore the clinical value of circulating EVs analysis we attempted a proof-of-concept in endometrial cancer (EC) with ExoGAG, an easy to use and highly efficient new technology to enrich EVs. Technical performance was first evaluated using EVs secreted by Hec1A cells. Then, the clinical value of this strategy was questioned by analyzing the levels of two well-known tissue biomarkers in EC, L1 cell adhesion molecule (L1CAM) and Annexin A2 (ANXA2), in EVs purified from plasma in a cohort of 41 EC patients and 20 healthy controls. The results demonstrated the specific content of ANXA2 in the purified EVs fraction, with an accurate sensitivity and specificity for EC diagnosis. Importantly, high ANXA2 levels in circulating EVs were associated with high risk of recurrence and non-endometrioid histology suggesting a potential value as a prognostic biomarker in EC. These results also confirmed ExoGAG technology as a robust technique for the clinical implementation of circulating EVs analyses. Keywords: EVs; ExoGAG; endometrial cancer; ANXA2 Author: Carolina Herrero, Alexandre de la Fuente, Carlos Casas-Arozamena, Victor Sebastian, Martin Prieto, Manuel Arruebo, Alicia Abalo, Eva Colás, Gema Moreno-Bueno, Antonio Gil-Moreno, Ana Vilar, Juan Cueva, Miguel Abal and Laura Muinelo-Romay Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Thu Dec 12 09:22:50 2019 CET ModDate: Thu Dec 12 09:22:50 2019 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3135710 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FDYFVT+URWPalladioL-Ital Type 1 Custom yes yes no 102 0 VCVIBQ+URWPalladioL-Bold Type 1 Custom yes yes no 103 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 104 0 VKLJVN+URWPalladioL-Roma Type 1 Custom yes yes no 105 0 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272 0 FGLHAD+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 273 0 FGLCKG+PalatinoLinotype TrueType WinAnsi yes yes no 274 0 FGLCNH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 275 0 FGLCOI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 276 0 FGLDLE+TimesNewRoman CID TrueType Identity-H yes yes yes 277 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 312 0 MFIGJL+Rpxb Type 1 Builtin yes yes no 325 0 FGLCKG+PalatinoLinotype TrueType WinAnsi yes yes no 331 0 FGLCNH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 332 0 FGLCOI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 333 0 FGLDLE+TimesNewRoman CID TrueType Identity-H yes yes yes 334 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 477 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-08-10 12:15:19 CEST RepresentationInformation: pmc_31842290.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-03-02 03:45:26 CET Size: 3135710 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 2 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐふひどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぃはのつどぴどはのづつぜ〴ぜ〰きづつどちぜ〴ぜ〰てひはねぜ〴ぜ〰ぅのつはねづぴひどちぬぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぐふひどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰こちねばぬづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぁひづぜ〴ぜ〰ぉのっひづちびづつぜ〴ぜ〰どのぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴ぜ〰はてぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐふひどてどづつぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ことはぷづつぜ〴ぜ〰いどちでのはびどびぜ〴ぜ〰ざちぬふづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはひひづぬちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ごふねはひぜ〴ぜ〰ぁででひづびびどぶづのづびびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: ぐふひどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぃはのつどぴどはのづつぜ〴ぜ〰きづつどちぜ〴ぜ〰てひはねぜ〴ぜ〰ぅのつはねづぴひどちぬぜ〴ぜ〰ぃちのっづひぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぐふひどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰こちねばぬづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぁひづぜ〴ぜ〰ぉのっひづちびづつぜ〴ぜ〰どのぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴ぜ〰はてぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐふひどてどづつぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ことはぷづつぜ〴ぜ〰いどちでのはびどびぜ〴ぜ〰ざちぬふづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはひひづぬちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ごふねはひぜ〴ぜ〰ぁででひづびびどぶづのづびびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぐふひどてどっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰こちねばぬづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぁひづぜ〴ぜ〰ぉのっひづちびづつぜ〴ぜ〰どのぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴ぜ〰はてぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐふひどてどづつぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ことはぷづつぜ〴ぜ〰いどちでのはびどびぜ〴ぜ〰ざちぬふづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはひひづぬちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ごふねはひぜ〴ぜ〰ぁででひづびびどぶづのづびびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰ぁひづぜ〴ぜ〰ぉのっひづちびづつぜ〴ぜ〰どのぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴ぜ〰はてぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐふひどてどづつぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ことはぷづつぜ〴ぜ〰いどちでのはびどびぜ〴ぜ〰ざちぬふづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはひひづぬちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ごふねはひぜ〴ぜ〰ぁででひづびびどぶづのづびびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぁぎじぁ〲ぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐふひどてどづつぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぅぃぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ことはぷづつぜ〴ぜ〰いどちでのはびどびぜ〴ぜ〰ざちぬふづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはひひづぬちぴづつぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ごふねはひぜ〴ぜ〰ぁででひづびびどぶづのづびびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぅざぜ〴ぜ〰ぐひはつふっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぉびはぬちぴどはのぜ〴ぜ〰てひはねぜ〴ぜ〰ぃはのつどぴどはのづつぜ〴ぜ〰きづつどふねぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸱ Children: Item: Title: ぐちぴどづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぅざぜ〴ぜ〰ぐひはつふっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぉびはぬちぴどはのぜ〴ぜ〰てひはねぜ〴ぜ〰ぃはのつどぴどはのづつぜ〴ぜ〰きづつどふねぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸱ Item: Title: ぅざぜ〴ぜ〰ぐひはつふっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰ぉびはぬちぴどはのぜ〴ぜ〰てひはねぜ〴ぜ〰ぃはのつどぴどはのづつぜ〴ぜ〰きづつどふねぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸱ Children: Item: Title: いどててづひづのぴどちぬぜ〴ぜ〰ぃづのぴひどてふでちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸴⸲⸲ Item: Title: ぅへはぇぁぇぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰ぉびはぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぃとちひちっぴづひどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰ちのつぜ〴ぜ〰が〱ぃぁきぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰こちねばぬづびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぉびはぬちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴ぜ〰てひはねぜ〴ぜ〰ぐぬちびねちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぃとちひちっぴづひどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰ちのつぜ〴ぜ〰が〱ぃぁきぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰こちねばぬづびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃとちひちっぴづひどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぅざびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰ぁぎじぁ〲ぜ〴ぜ〰ちのつぜ〴ぜ〰が〱ぃぁきぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰こちねばぬづびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぁぎじぁ〲ぜ〴ぜ〰ちのつぜ〴ぜ〰が〱ぃぁきぜ〴ぜ〰がづぶづぬびぜ〴ぜ〰どのぜ〴ぜ〰ぐぬちびねちぜ〴ぜ〰こちねばぬづびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃどひっふぬちぴどのでぜ〴ぜ〰ぅざびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: MFIGJL+Rpxb FontSubset: true FirstChar: 47 LastChar: 47 FontDescriptor: FontName: MFIGJL+Rpxb Flags: Symbolic FontBBox: -57, -266, 932, 729 FontFile: true Font: BaseFont: FDYFVT+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: FDYFVT+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: VCVIBQ+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: VCVIBQ+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: 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