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

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.

Bulk IgG glycosylation predicts COVID-19 severity and vaccine antibody response.

Although vaccination efforts have expanded, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2. Measuring IgG Fc glycosylation provides insight into an infected individual's inflammatory state, among other functions. We set out to interrogate bulk IgG glycosylation changes from SARS-CoV-2 infection and vaccination, using plasma from mild or hospitalized COVID-19 patients, and from vaccinated individuals.

Dynamic Monitoring of Seroconversion using a Multianalyte Immunobead Assay for Covid-19.

Multiplex technologies for interrogating multiple biomarkers in concert have existed for several decades; however, methods to evaluate multiple epitopes on the same analyte remain limited. This report describes the development and optimization of a multiplexed immunobead assay for serological testing of common immunoglobulin isotypes (e.g.

Predictors of HbA1c among Adipocytokine Biomarkers in African-American Men with Varied Glucose Tolerance.

This study explored adipocytokine associations with acute and chronic hyperglycemia in African-American men (AAM). Fourteen adipocytokines were measured from men with normal glucose tolerance (NGT) or type 2 diabetes (T2D, drug-naïve MF(-) or using metformin MF(+)). Acute and chronic hyperglycemia were evaluated by 120 min oral glucose tolerance test (OGTT) and glycohemoglobin A1c (HbA1c).

Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions.

Background: This study explores the potential diagnostic utility of soluble Human Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma and benign lung lesions.

Methods: Conditioned media from the NSCLC cell lines H358 and H1703 were immunoblotted for soluble isoforms of major histocompatibility complex (MHC) class I (ABC) and II (DRB1, DMB, and DQ) antigens. Sera from 25 patients with benign and 25 patients with malignant lesions were similarly evaluated to appraise the potential diagnostic value.

The serum-based VeriStrat® test is associated with proinflammatory reactants and clinical outcome in non-small cell lung cancer patients.

Background: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research. The aim of this study was to correlate VeriStrat status with other circulating biomarkers in advanced NSCLC patients - each with respect to clinical outcomes.

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

Background: Angiogenesis is associated with tumor progression in a range of malignancies. Herein, we develop custom immunobead assays for several mechanistically important targets and evaluated these against sera from cohorts of non-small cell lung cancer (NSCLC) patients.

Methods: Antigen "capture" antibodies for midkine, syndecan-1, and ANGPTL4 were independently conjugated to MagPlex® Microspheres using standard carbodiimide/NHS-based chemistry.

Serum Biomarkers May Prognosticate Recurrence in Node-Negative, Non-Small Cell Lung Cancers Less Than 4 Centimeters.

Background: A significant proportion of patients who undergo lung resection for less than 4 cm non-small cell lung cancer (NSCLC) will die of disease recurrence within 5 years. The ability to identify patients at greatest risk for recurrence may help individualize treatment and surveillance regimens and improve outcomes. We hypothesized that a serum-based biomarker panel could help risk stratify patients with node-negative NSCLC less than 4 cm for recurrence after lung resection.

Differential expression of circulating biomarkers of tumor phenotype and outcomes in previously treated non-small cell lung cancer patients receiving erlotinib vs. cytotoxic chemotherapy.

Background: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination.

Methods: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79). Known EGFR mutation positive cases were excluded from analysis.

Anti-vimentin Antibodies Present at the Time of Transplantation May Predict Early Development of Interstitial Fibrosis/Tubular Atrophy.

Background: Anti-vimentin (a cytoskeletal protein) autoantibodies in renal transplant recipients have been correlated with interstitial fibrosis/tubular atrophy (IFTA). In this study, we examine the association between pretransplantation anti-vimentin antibodies and the subsequent development of IFTA.

Methods: Sera obtained before renal transplantation from 97 transplant recipients were analyzed for the presence of anti-vimentin antibodies via Luminex assays to determine the concentration of anti-vimentin antibodies.

Angiogenesis Biomarkers May Be Useful in the Management of Patients With Indeterminate Pulmonary Nodules.

Background: Low-dose computed tomography (CT) lung cancer screening is known to have a high false positive rate. This study aims to survey biomarkers of angiogenesis for those capable of assigning clinical significance to indeterminate pulmonary nodules detected through CT imaging studies.

Methods: An institutional database and specimen repository was used to identify 193 patients with stage I non-small cell lung cancer (T1N0M0) and 110 patients with benign solitary pulmonary nodules detected by CT imaging studies.

Value of circulating insulin-like growth factor-associated proteins for the detection of stage I non-small cell lung cancer.

Objective: Circulating biomarkers related to insulin-like growth factor (IGF) signaling are associated with disease progression in multiple carcinomas, but their potential diagnostic value for lung cancer screening has been inadequately examined. We evaluated 9 circulating IGF-related factors for their ability to assign clinical significance to indeterminate pulmonary nodules identified via computed tomography-based radiologic studies.

Methods: Patients (n = 224 stage I non-small cell lung cancer; n = 123 benign) were enrolled by Rush University and the Mayo Clinic and had pretreatment serum evaluated for levels of IGF-1, IGF-2, and insulin-like growth factor binding proteins (IGFBPs) 1-7.

Circulating angiogenesis biomarkers are associated with disease progression in lung adenocarcinoma.

Background: Dysregulation of angiogenesis is known to be associated with tumorigenesis and metastatic progression in multiple carcinomas. The aim of this study was to evaluate the prognostic value of circulating angiogenesis biomarkers in lung adenocarcinoma progression. For that, we hypothesize that circulating levels of biomarkers characteristic for discrete processes within angiogenesis are associated with specific phases of disease progression.

Development of a bead-based immunoassay to routinely measure vimentin autoantibodies in the clinical setting.

Introduction: Vimentin is an intermediate filament protein generally expressed in the cytosol of many adult cell types, including leukocytes, fibroblasts and endothelial cells. Several tissue and/or injury-specific isoforms of vimentin are known to exist that may trigger autoimmune responses due to aberrant structural or conformational variations. Such scenarios include allograft rejection and certain autoimmune diseases, such as rheumatoid arthritis.

Development and validation of a plasma biomarker panel for discerning clinical significance of indeterminate pulmonary nodules.

Introduction: The recent findings of the National Lung Screening Trial showed 24.2% of individuals at high risk for lung cancer having one or more indeterminate nodules detected by low-dose computed tomography-based screening, 96.4% of which were eventually confirmed as false positives.

Development of a serum biomarker panel predicting recurrence in stage I non-small cell lung cancer patients.

Objective: Molecular diagnostics capable of prognosticating disease recurrence in stage I non-small cell lung cancer (NSCLC) patients have implications for improving survival. The objective of the present study was to develop a multianalyte serum algorithm predictive of disease recurrence in stage I NSCLC patients.

Methods: The Luminex immunobead platform was used to evaluate 43 biomarkers against 79 patients with resectable NSCLC, with the following cohorts represented: stage I (T(1)-T(2)N(0)M(0)) NSCLC without recurrence (n = 37), stage I (T(1)-T(2)N(0)M(0)) NSCLC with recurrence (n = 15), and node-positive (T(1)-T(2)N(1)-N(2)M(0)) NSCLC (n = 27).

Biomarkers of the insulin-like growth factor pathway predict progression and outcome in lung cancer.

Background: Insulin-like growth factor 1 (IGF-I), IGF binding proteins (IGFBP) 1 to 7, and C-peptide have been postulated to predict survival in non-small cell lung cancer (NSCLC). Studying serum levels in NSCLC patients treated with surgical resection may provide information on the aggressiveness of tumors and be predictive of disease recurrence.

Methods: Immunobead assays were used to measure pretreatment serum levels of IGF-I, IGFBP1 to IGFBP7, and C-peptide in 100 NSCLC patients.

Enhancement of a multianalyte serum biomarker panel to identify lymph node metastases in non-small cell lung cancer with circulating autoantibody biomarkers.

We recently reported the development of a multianalyte serum algorithm to identify nodal status in non-small cell lung cancer (NSCLC) patients facing an anatomic resection with curative intent. This study aims to enhance the overall performance characteristics of this test by adding autoantibody biomarkers identified through immunoproteomic discovery. More specifically, we used sera from 20 NSCLC patients to probe 2-D immunoblots of HCC827 lysates for tumor-associated autoantigens.

Oral glucosamine modulates the response of the liver and lymphocytes of the mesenteric lymph nodes in a papain-induced model of joint damage and repair.

Objectives: To assess whether glucosamine (GlcN), an oral supplement commonly taken to relieve the symptoms of osteoarthritis, modulates the immune and inflammatory responses to joint injury in organs proximal to GlcN absorption; namely, the liver and the gut-draining lymph nodes.

Method: Using a papain-injected knee mouse model, standard histological methods were used to validate our model and document the impact of GlcN (100mg/kg/day) on groups of C57BL/6 mice (n=5). Circulating inflammatory cytokines were assessed by Luminex-based immunoassays and the relevance of this cytokine profile on proteoglycan biosynthesis evaluated using a patellar-cartilage assay.

Establishment of a multi-analyte serum biomarker panel to identify lymph node metastases in non-small cell lung cancer.

Introduction: In non-small cell lung cancer (NSCLC), the presence of locoregional lymph node metastases remains the most important prognostic factor and significantly guides treatment regimens. Unfortunately, currently-available noninvasive staging modalities have limited accuracy. The objective of this study was to create a multianalyte blood test capable of discriminating a patient's true (pathologic) nodal status preoperatively.