Development of bead based multiplexed immunoassay for evaluation of midkine, syndecan-1, and ANGPTL4 in patient serum

Tarhoni, Imad; Fhied, Cristina; Pool, Mark; Liptay, Michael J.; Bonomi, Philip; Seder, Christopher W.; Borgia, Jeffrey A.

doi:10.1080/15321819.2017.1407338

Cited by 8 publications

(4 citation statements)

References 18 publications

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“…ProcartaPlex TM immunoassays incorporate magnetic microsphere technology licensed from Luminex TM to enable the simultaneous detection and quantitation of multiple protein targets in diverse matrices. In cases where commercially available assays are not available, the Luminex platform is superior to many other multiplex immunoassay platforms because custom assays can be developed with relative ease 14 …”

Section: Discussionmentioning

confidence: 99%

“…In cases where commercially available assays are not available, the Luminex platform is superior to many other multiplex immunoassay platforms because custom assays can be developed with relative ease. 14 The platform allows the simultaneous detection from a single sample of up to 80 protein targets on the Luminex TM 200 TM and FLEXMAP 3D TM platform and 50 protein targets on the MAGPIX TM platform.…”

Section: Discussionmentioning

confidence: 99%

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A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

Peng¹,

Zhang

Rui³

et al. 2022

Clinical Laboratory Analysis

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Background Immunotherapy was widely used for the treatment of non‐small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC. Methods Serum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta‐Plex Human Immuno‐Oncology Checkpoint Panel. Results The expression levels of sTIM‐3, sCD137, sCD27, sLAG‐3, sIDO, sPD‐L2, sCD152, sCD80, and sPD‐1 were all significantly increased in serum of NSCLC patients. Especially, sLAG‐3 was significantly elevated in serum of NSCLC patients at early‐stage (stages I and II), TIM‐3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early‐stage groups. Receiver operating characteristics (ROC) results showed that except for PD‐1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM‐3 had the highest diagnostic accuracy, followed by sLAG‐3. Combining sTIM‐3, sLAG‐3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM‐3 and sIDO were correlated with stage and age, respectively. Conclusions TIM‐3 and LAG‐3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM‐3, LAG‐3, and CD137 could increase the diagnostic accuracy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

Peng¹,

Zhang

Rui³

et al. 2022

Clinical Laboratory Analysis

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“…Therefore, the expression and mechanism of ANGPTL4 may be related to tumor type. Tarhoni et al [ 97 ] first developed custom immunobead assays for several mechanistically important targets and evaluated these against sera from a patient cohort with non-small cell lung cancer (NSCLC). They successfully developed and analytically validated a triplex immunobead assay for the quantitation of midkine, syndecan-1, and ANGPTL4 from patient sera which will be an important tool for future studies delineating the role of angiogenesis in lung cancer progression [ 97 ].…”

Section: Functions Of Angptl4mentioning

confidence: 99%

A review of the multifunctionality of angiopoietin-like 4 in eye disease

Yang

Cheng

2018

Bioscience Reports

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Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine regulating vascular permeability, angiogenesis, and inflammation. Dysregulations in these responses contribute to the pathogenesis of ischemic retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion, and sickle cell retinopathy (SCR). However, the role of ANGPTL4 in these diseases remains controversial. Here, we summarize the functional mechanisms of ANGPTL4 in several diseases. We highlight original studies that provide detailed data about the mechanisms of action for ANGPTL4, its applications as a diagnostic or prognostic biomarker, and its use as a potential therapeutic target. Taken together, the discussions in this review will help us gain a better understanding of the molecular mechanisms by which ANGPTL4 functions in eye disease and will provide directions for future research.

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“…This resulted in a total of 26 biomarkers of interest for further assessment via targeted Luminex assays. A custom Luminex immunobead assay was built for each of the 26 selected targets using methods we previously reported [ 16 , 17 , 18 ]. Briefly, assay construction was accomplchemistryconjugation of each recombinant protein (antigen) on a unique MagPlex bead region via standard sulfo-NHS/EDC chemistries.…”

Section: Methodsmentioning

confidence: 99%

Development of a Novel Circulating Autoantibody Biomarker Panel for the Identification of Patients with ‘Actionable’ Pulmonary Nodules

Auger

Moudgalya

Neely

et al. 2023

Cancers

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Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology’s Lung Imaging and Reporting Data System (Lung-RADS) 80–90% of patients screened will have clinically “non-actionable” nodules (Lung-RADS 1 or 2), and those harboring larger, clinically “actionable” nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.

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Development of bead based multiplexed immunoassay for evaluation of midkine, syndecan-1, and ANGPTL4 in patient serum

Abstract: We successfully developed and analytically validated a 3-plex immunobead assay for quantifying midkine, syndecan-1, and ANGPTL4 in patient sera. This multiplexed assay will provide an important tool for future studies delineating the role of angiogenesis in lung cancer progression.

Cited by 8 publications

References 18 publications

A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

A review of the multifunctionality of angiopoietin-like 4 in eye disease

Development of a Novel Circulating Autoantibody Biomarker Panel for the Identification of Patients with ‘Actionable’ Pulmonary Nodules

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