Discovery and Validation of Novel Protein Biomarkers in Ovarian Cancer Patient Urine

Sandow, Jarrod J.; Rainczuk, Adam; Infusini, Giuseppe; Makanji, Ming; Bilandzic, Maree; Wilson, Amy L.; Fairweather, Nicole; Stanton, Peter G.; Garama, Daniel J.; Gough, Daniel; Jobling, Thomas W.; Webb, Andrew I.; Stephens, Andrew N.

doi:10.1002/prca.201700135

Cited by 43 publications

(36 citation statements)

References 54 publications

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“…Label-free MS protocols are advantageous because of their capacity to detect rare peptides in samples with a high dynamic range of quantification, especially when substantial changes in protein content are investigated [13,15,16]. Label-free quantitative LC-MS/MS has proven useful in the discovery of markers for ovarian [17], breast [18], gastric [19] and colorectal [20] cancers, but not yet for pediatric HL.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Repetto

Mussolin

et al. 2020

IJMS

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The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12–16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered “differentially abundant”. LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen β and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL.

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Section: Introductionmentioning

confidence: 99%

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Repetto

Mussolin

et al. 2020

IJMS

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“…Esta investigación fue realizada para evaluar la utilidad de HE4 en la detección precoz de cáncer ovárico de células epiteliales comparándolo frente a CA125 e índice ROMA, para los cuales se consideró puntos de corte preestablecidos en cada variable a evaluar. Diferentes estudios sugieren que HE4 es superior a CA125 para distinguir entre enfermedades ováricas malignas y benignas [22][23][24][25][26][27]. Los resultados muestran que HE4 presenta un valor medio altamente diferenciable, que permite distinguir entre mujeres con masas pélvicas malignas de las benignas (7.19 versus 5.71; control 5.79), al contrario de CA125 e I. ROMA (5.72 versus 4.64; control 4.57 y 5.92 versus 2.29; control 3.50, respectivamente).…”

Section: Discussionunclassified

Utilidad de la Proteína Epididimal Humana 4 (HE4) en la detección de Cáncer de ovario.

Nájera¹,

Morey-León

Salas

et al. 2018

Rev. Oncol. Ecu

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Introducción: El cáncer de ovario epitelial aunque tiene baja prevalencia está considerado entre las malignidades ginecológicas más letales por su alta mortalidad. El interés en la detección temprana del cáncer de ovario como mecanismo para lograr la reducción de la mortalidad ha crecido con el descubrimiento de biomarcadores tumorales séricos asociados a tumores malignos. El presente estudio plantea determinar la eficacia del uso del biomarcador HE4 para la detección precoz de cáncer epitelial de ovario en estadios tempranos. Métodos: Se evaluaron pacientes con masas pélvicas entre abril de 2015 y marzo de 2016. Valores de sensibilidad, especificidad, predictivo positivo y negativo, razón de probabilidad positiva y negativa, y pruebas estadísticas fueron calculados para determinar la relación entre los estados menopáusicos, y los grupos de acuerdo con el resultado histológico (benigno, maligno y control) de HE4, CA125 y ROMA. Resultados: Ingresaron al estudio 53 pacientes. La proteína epididimal humana 4 - HE4 presentó un valor medio diferenciable que permite distinguir masas pélvicas malignas (HE4:7,19 (maligno) vs. 5,71 (benigno)), igualmente la combinación HE4 + ROMA presentan mayor sensibilidad y especificidad (S: 100 %; E: 94.29 %) que las combinaciones CA125 + HE4 y CA125 + ROMA (S: 80 % y 88.89 %; E: 75.76 % y 77.14 %). Conclusión: Los resultados sugieren que HE4 serviría como un biomarcador eficiente para la diferenciación de masas pélvicas en estadios tempranos y si se adiciona el estatus menopaúsico, e índice ROMA afianzaría los resultados, permitiendo la diferenciación del cáncer de ovario epitelial en estadios tempranos en el país.

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“…Furthermore, RAW mass spectrometry data were also analyzed with MaxQuant (version 1.6.0.16) using more stringent criteria for peptide/protein identification, as an alternative to the abovementioned approach. Analysis was performed as previously described with some minor modifications. List of identified proteins is presented in Table S2, Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

Intrasurgical Protein Layer on Titanium Arthroplasty Explants: From the Big Twelve to the Implant Proteome

Jäger

Jennissen

Haversath

et al. 2019

Proteomics Clinical Apps

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Purpose: Aseptic loosening in total joint replacement due to insufficient osteointegration is an unsolved problem in orthopaedics. The purpose of the study is to obtain a picture of the initial protein adsorption layer on femoral endoprosthetic surfaces as the key to the initiation of osseointegration. Experimental design: The paper describes the first study of femoral stem explants from patients for proteome analysis of the primary protein layer. After 2 min in situ, the stems are explanted and frozen in liquid nitrogen. Proteins are eluted under reducing conditions and analyzed by LC-MS/MS. Results: After exclusion of proteins identified by a single peptide, the implant proteome is found to consist of 2802 unique proteins. Of these, 77% are of intracellular origin, 9% are derived from the plasma proteome, 8% from the bone proteome, and four proteins with highest specificity score could be assigned to the bone marrow proteome (transcriptome). The most abundant protein in the adsorbed total protein layer is hemoglobin (8-11%) followed by serum albumin (3.6-6%). Conclusions: A detailed knowledge of the initial protein film deposited onto the implants, as demonstrated here for the first time, may help to understand and predict the response of the osseous microenvironment to implant surfaces.

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Discovery and Validation of Novel Protein Biomarkers in Ovarian Cancer Patient Urine

Abstract: This is the first application of a LFQ-PRM workflow to identify and validate ovarian cancer-specific biomarkers in patient urine samples.

Cited by 43 publications

References 54 publications

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Utilidad de la Proteína Epididimal Humana 4 (HE4) en la detección de Cáncer de ovario.

Intrasurgical Protein Layer on Titanium Arthroplasty Explants: From the Big Twelve to the Implant Proteome

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