Biomarker discovery

Cancer cachexia (CC) is a devastating metabolic syndrome characterized by skeletal muscle wasting and body weight loss, posing a significant burden on the health and survival of cancer patients. Despite ongoing efforts, effective treatments for CC are still lacking. Metabolomics, an advanced omics technique, offers a comprehensive analysis of small-molecule metabolites involved in cellular metabolism. In CC research, metabolomics has emerged as a valuable tool for identifying diagnostic biomarkers, unravelling molecular mechanisms and discovering potential therapeutic targets...

Non-coding RNAs (ncRNAs) are an assorted collection of transcripts that are not translated into proteins. Since their discovery, ncRNAs have gained prominence as crucial regulators of various biological functions across diverse cell types and tissues, and their abnormal functioning has been implicated in disease. Notably, extensive research has focused on the relationship between microRNAs (miRNAs) and human cancers, although other types of ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as significant contributors to human disease...

BACKGROUND: Diabetic eye disease is a highly prevalent and sight-threatening disorder. It is a disease of neuro-vascular unit of the retina, if left untreated can cause blindness. Therapeutic approaches followed for its treatment can only restrict the progression of the disease with highly variable results. There is no known biomarker for an early diagonsis of this disease, therefore by the time it is detected it goes beyond repair. This creates a massive demand for development of such biomarkers that help detect disease in its earlier stages...

BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals...

BACKGROUND: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy...

Environmental chemical exposures influence immune system functions, and humans are exposed to a wide range of chemicals, termed the chemical "exposome". A comprehensive, discovery analysis of the associations of multiple chemical families with immune biomarkers is needed. In this study, we tested the associations between environmental chemical concentrations and immune biomarkers. We analyzed the United States cross-sectional National Health and Nutrition Examination Survey (NHANES 1999-2018). Chemical biomarker concentrations were measured in blood or urine (196 chemicals, 17 chemical families)...

Cerebral palsy (CP) is the most common disabling disease in children, and motor dysfunction is the core symptom of CP. Although relevant risk factors have been found to be closely associated with CP: congenital malformations, multiple gestation, prematurity, intrauterine inflammation and infection, birth asphyxia, thrombophilia, and perinatal stroke. Its important pathophysiological mechanism is amniotic fluid infection and intraamniotic inflammation leading to fetal developing brain damage, which may last for many years...

BACKGROUND: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes. METHODS: We present an integrated analysis of 4,091 proteins and 630 metabolites in the Chronic Renal Insufficiency Cohort Study (N=1,708; average follow-up for kidney failure [KF], 9.5 years, with 537 events). Proteins and metabolites were integrated using an unsupervised clustering method and we assessed associations between clusters and CKD progression and kidney failure using Cox proportional hazards models...

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized for its global prevalence and potential progression to more severe liver diseases such as non-alcoholic steatohepatitis (NASH). The gut microbiota plays a pivotal role in the pathogenesis of NAFLD, yet the detailed characteristics and ecological alterations of gut microbial communities during the progression from non-alcoholic fatty liver (NAFL) to NASH remain poorly understood. Methods: In this study, we conducted a comparative analysis of gut microbiota composition in individuals with NAFL and NASH to elucidate differences and characteristics...

BACKGROUND: The anti-IgE monoclonal, omalizumab, is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during one year of omalizumab treatment. METHODS: 1-year, open-label, S tudy o f M echanisms of action of O malizumab in S evere A sthma ( SoMOSA ) involving 216 severe (GINA step 4/5) uncontrolled atopic asthmatics (≥2 severe exacerbations in previous year) on high-dose inhaled corticosteroids, long-acting β-agonists, ± mOCS...

Imaging agents for positron emission tomography (PET) and single-photon emission computerized tomography (SPECT) have shown their utility in many situations, answering clinical questions related to drug development and medical considerations. The discovery and development of imaging agents follow a well-understood process, with variations related to available starting points and to the envisaged imaging application. This article describes the general development path leading from the expression of an imaging need and project initiation to a clinically usable imaging agent...

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors...

Discovery research is the starting point for the development of more effective anti-cancer treatments. It requires an interdisciplinary research environment with first-class infrastructural support in which curiosity-driven research can lead to new concepts for treating cancer. Translating such research findings to clinical practice requires complementary skills and infrastructures, including high-quality clinical facilities, access to patient cohorts and participation of pharma. This complex ecosystem has yielded many new but also "me too" treatment regimens, especially in immuno-oncology resulting in an extremely high pricing of anti-cancer agents...

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the body's ability to counteract their harmful effects, playing a key role in the pathogenesis of brain and lung-related diseases. This review comprehensively examines the intricate mechanisms by which oxidative stress influences cellular and molecular pathways, contributing to neurodegenerative, cardiovascular, and respiratory disorders. Emphasizing the detrimental effects on both brain and lung health, we discuss innovative diagnostic biomarkers, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), and the potential of antioxidant therapies...

Electronic health records (EHRs) coupled with large-scale biobanks offer great promises to unravel the genetic underpinnings of treatment efficacy. However, medication-induced biomarker trajectories stemming from such records remain poorly studied. Here, we extract clinical and medication prescription data from EHRs and conduct GWAS and rare variant burden tests in the UK Biobank (discovery) and the All of Us program (replication) on ten cardiometabolic drug response outcomes including lipid response to statins, HbA1c response to metformin and blood pressure response to antihypertensives (N = 740-26,669)...

Allogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies, however it can also result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier to reduce incidence of aGVHD by improving donor selection. Genome-wide DNA methylation was assessed in a discovery cohort of 288 HCT donors selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD...

BACKGROUND: The Multi-System Inflammatory Syndrome in Children (MIS-C) can develop several weeks after SARS-CoV-2 infection and requires a distinct treatment protocol. Distinguishing MIS-C from SARS-CoV-2 negative sepsis (SCNS) patients is important to quickly institute the correct therapies. We performed targeted proteomics and machine learning analysis to identify novel plasma proteins of MIS-C for early disease recognition. METHODS: A case-control study comparing the expression of 2,870 unique blood proteins in MIS-C versus SCNS patients, measured using proximity extension assays...

Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening...

BACKGROUND: Gastric cancer (GC) is characterized by high morbidity, high mortality and low early diagnosis rate. Early diagnosis plays a crucial role in radically treating GC. The aim of this study was to identify plasma biomarkers for GC and early GC diagnosis. METHODS: We quantified 369 protein levels with plasma samples from discovery cohort (n = 88) and validation cohort (n = 50) via high-throughput proximity extension assay (PEA) utilizing the Olink-Explore-384-Cardiometabolic panel...

Numerous Pseudomonas species can infect aquatic animals, such as farmed rainbow trout, sea trout, sea bass, and sea bream, by causing disease or stress reactions. In aquaculture facilities, a number of Pseudomonas species have been isolated and identified as the main pathogens. The present study describes the characterization of 18 Pseudomonas strains, isolated from fish products using shotgun proteomics. The bacterial proteomes obtained were further analyzed to identify the main functional pathway proteins involved...