Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer.

Background: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.

Methods: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.

Results: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity.

Discovery of novel glioma serum biomarkers by proximity extension assay.

Background: Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the future availability of new disease-modifying treatments.

Mucin 13 (MUC13) as a candidate biomarker for ovarian cancer detection: potential to complement CA125 in detecting non-serous subtypes.

Objectives: Ovarian cancer is the most lethal gynecological malignancy in developed countries. One of the key associations with the high mortality rate is diagnosis at late stages. This clinical limitation is primarily due to a lack of distinct symptoms and detection at the early stages.

Quantitation of cardiac troponin I in cancer patients treated with immune checkpoint inhibitors: a case-control study.

Objectives: Immune checkpoint inhibitors (ICIs) cause a variety of toxicities, including immune-related adverse events (irAEs), but there are no biomarkers to predict their development. Guidelines recommend measuring circulating cardiac troponin I (cTnI) during ICI therapy to detect related cardiotoxicities. Moreover, elevated cTnI has also been associated with worse outcomes in non-cardiac patients, including cancer.

Sensitive Serology Measurements in the Saliva of Individuals with COVID-19 Symptoms Using a Multiplexed Immunoassay.

Background: There are numerous benefits to performing salivary serology measurements for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen for coronavirus disease 2019 (COVID-19). Here, we used a sensitive multiplex serology assay to quantitate salivary IgG against 4 SARS-CoV-2 antigens: nucleocapsid, receptor-binding domain, spike, and N-terminal domain.

Methods: We used single samples from 90 individuals with COVID-19 diagnosis collected at 0 to 42 days postsymptom onset (PSO) and from 15 uninfected control subjects.

Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis.

Kallikrein-related peptidases (KLKs) are implicated in many cancer-related processes. KLK6, one of the 15 KLK family members, is a promising biomarker for diagnosis of many cancers and has been associated with poor prognosis of colorectal cancer (CRC) patients. Herein, we evaluated the expression and cellular functions of KLK6 in colon cancer-derived cell lines and in clinical samples from CRC patients.

Transcriptome profiling and proteomic validation reveals targets of the androgen receptor signaling in the BT-474 breast cancer cell line.

Background: Accumulating evidence suggests that the androgen receptor (AR) and its endogenous ligands influence disease progression in breast cancer (BCa). However, AR-mediated changes in BCa differ among the various BCa subtypes according to their hormone receptor profile [i.e.

Electronic field effect detection of SARS-CoV-2 N-protein before the onset of symptoms.

As part of the efforts to contain the pandemic, researchers around the world have raced to develop testing platforms to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the Coronavirus disease 2019 (COVID-19). Within the different detection platforms studied, the field effect transistor (FET) is a promising device due to its high sensitivity and fast detection capabilities. In this work, a graphene-based FET which uses a boron and nitrogen co-doped graphene oxide gel (BN-GO gel) transducer functionalized with nucleoprotein antibodies, has been investigated for the detection of SARS-CoV-2 nucleocapsid (N)-protein in buffer.

Patients with severe COVID-19 do not have elevated autoantibodies against common diagnostic autoantigens.

Objectives: Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19) presents occasionally with an aberrant autoinflammatory response, including the presence of elevated circulating autoantibodies in some individuals. Whether the development of autoantibodies against self-antigens affects COVID-19 outcomes remains unclear. To better understand the prognostic role of autoantibodies in COVID-19, we quantified autoantibodies against 23 markers that are used for diagnosis of autoimmune disease.

Ultrasensitive assay for saliva-based SARS-CoV-2 antigen detection.

Objectives: Widespread SARS-CoV-2 testing is invaluable for identifying asymptomatic/pre-symptomatic individuals. There remains a technological gap for highly reliable, easy, and quick SARS-CoV-2 diagnostic tests suitable for frequent mass testing. Compared to nasopharyngeal (NP) swab-based tests, saliva-based methods are attractive due to easier and safer sampling.

Comparison of two multiplexed technologies for profiling >1,000 serum proteins that may associate with tumor burden.

 In this pilot study, we perform a preliminary comparison of two targeted multiplex proteomics technologies for discerning serum protein concentration changes that may correlate to tumor burden in ovarian cancer (OC) patients. : Using the proximity extension assay (PEA) and Quantibody® Kiloplex Array (QKA), we measured >1,000 proteins in the pre-surgical and post-surgical serum from nine OC patients (N=18 samples). We expect that proteins that have decreased significantly in the post-surgical serum concentration may correlate to tumor burden in each patient.

Plasma Protein Profiling by Proximity Extension Assay Technology Reveals Novel Biomarkers of Traumatic Brain Injury-A Pilot Study.

Background: Traumatic brain injury (TBI) is a significant public health issue affecting nearly 69 million patients worldwide per year. Reliable diagnostic biomarkers are urgently needed to aid in disease diagnosis and prognosis and to guide patient aftercare. Blood biomarkers represent an attractive modality to quickly, cheaply, and objectively evaluate clinical status.

Predicting response and toxicity to PD-1 inhibition using serum autoantibodies identified from immuno-mass spectrometry.

Validated biomarkers are needed to identify patients at increased risk of immune-related adverse events (irAEs) to immune checkpoint blockade (ICB). Antibodies directed against endogenous antigens can change after exposure to ICB. Patients with different solid tumors stratified into cohorts received pembrolizumab every 3 weeks in a Phase II trial (INSPIRE study).

Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden.

To account for cancer heterogeneity, we previously introduced the concept of "personalized" tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual patients, but the reliability of the technologies remains to be tested for this purpose. Here, we sought to explore the potential of a novel proteomics platform, which utilizes a multiplexed antibody microarray, to detect changes in serum protein concentration that may correlate to tumor burden in pancreatic cancer.

Utility of a Fifth-Generation Ultrasensitive Prostate-Specific Antigen Assay for Monitoring Prostate Cancer Patients after Radical Prostatectomy with 3 Years of Follow-Up.

Background: We investigated an ultrasensitive prostate-specific antigen (uPSA) immunoassay (MesoScale; lower limit of detection (LLD) of 0.0035 pg/mL) to monitor patients with prostate cancer (PCa) following radical prostatectomy (RP) and to examine whether changes in PSA in the conventionally undetectable range (<1 pg/mL) can predict biochemical relapse (BCR).

Methods: We measured uPSA in serial serum samples (N = 100) collected from 20 RP cases with a third-generation ELISA (LLD of 1 pg/mL) and the fifth-generation MesoScale assay.

Mass Spectrometry-Based Assay for Targeting Fifty-Two Proteins of Brain Origin in Cerebrospinal Fluid.

Cerebrospinal fluid (CSF) is a circulatory fluid of the central nervous system and it can reflect the biochemical changes occurring in the brain. Although CSF retrieval through lumbar puncture is invasive, it remains the most commonly used fluid in exploring brain pathology as it is less complex and contains a higher concentration of brain-derived proteins than plasma (Reiber, H. 2001, 310, 173-186; Macron et al.

Discovery of novel plasma biomarker ratios to discriminate traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability. Despite increased awareness, reliable biomarkers are urgently needed to aid in all forms of traumatic brain injury diagnosis and prognosis. Here, we aim to assess the diagnostic utility of known and novel TBI biomarkers in a pilot patient cohort of severe TBI (sTBI) patients and healthy controls.

Kallikrein-related peptidases protein expression in lymphoid tissues suggests potential implications in immune response.

Objectives: Kallikrein-related peptidases (KLKs) are a subgroup of 15 secreted chymotrypsin- and trypsin-like serine proteases that have been reported to possess novel functions in innate immunity and inflammation. Since the potential role of KLKs in immunity has not been studied in detail at the protein level, we examined the expression pattern of 12 members of the KLK family in immune-related tissues.

Design & Methods: Protein expression in tissue extracts was evaluated using immunoassays (ELISA).

Kallikrein-related peptidases 6 and 10 are elevated in cerebrospinal fluid of patients with Alzheimer's disease and associated with CSF-TAU and FDG-PET.

Background: Alterations in the expression of human kallikrein-related peptidases (KLKs) have been described in patients with Alzheimer's disease (AD). We elucidated the suitability of KLK6, KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers.

Methods: KLK levels in cerebrospinal fluid (CSF), as determined by ELISA, were compared between 32 AD patients stratified to A/T/(N) system with evidence for amyloid pathology and of 23 normal controls with normal AD biomarkers.

Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer's disease.

Background Alzheimer's disease (AD) is the most prevalent form of dementia. Currently, the most studied biomarkers of AD are cerebrospinal fluid (CSF) amyloid β 1-42, total tau and phosphorylated tau. However, misdiagnosis can exceed 20%.

Serum PD-1 Is Elevated after Pembrolizumab Treatment but Has No Predictive Value.

Immune-checkpoint blockade (ICB) uses antibody targeting of specific inhibitory receptors and ligands. The major limitations of ICB, such as high cost, limited success rate, and immune-related adverse events (irAE), highlight the need for predictive biomarkers. We analyzed pre-immunotherapy and post-immunotherapy serum samples of 24 patients treated with pembrolizumab for changes in PD-1 and over 1,000 additional protein markers using a multiplex proximity extension assay (PEA) to identify potential predictive biomarkers of response and/or toxicity.

Correction to: A proteome-wide immuno-mass spectrometric identification of serum autoantibodies.

[This corrects the article DOI: 10.1186/s12014-019-9246-0.].

A proteome-wide immuno-mass spectrometric identification of serum autoantibodies.

Background: Autoantibodies are produced when tolerance to self-antigens is broken and they can be mediators of tissue injury and systemic inflammation. They are excellent biomarkers because they are minimally invasive to screen and are highly abundant in serum due to limited proteolysis and slow clearance. Conventionally used methods of identifying autoantibodies in patient sera include indirect immunofluorescence, enzyme-linked immunoabsorbent assays (ELISAs) and protein microarrays.

Expression profile of human tissue kallikrein 15 provides preliminary insights into its roles in the prostate and testis.

Background: Human tissue kallikrein 15 (KLK15) is the latest member of the kallikrein-related peptidase family. Little is known about the pathophysiological roles of KLK15. Previous studies implied a role of KLK15 in prostate cancer.