Proteomics. Clinical Applications

PURPOSE: Despite recent advancements in our understanding of driver gene mutations and heterogeneity within brain tumors, whether primary or metastatic (also known as secondary), our comprehension of proteomic changes remains inadequate. The aim of this study is to provide an informative source for brain tumor researches, and distinguish primary brain tumors and secondary brain tumors from extracranial origins based on proteomic analysis. EXPERIMENTAL DESIGN: We assembled the most frequent brain tumors as follows: gliomas from WHO grade 2 to 4, with IDH1 mutations and wildtypes; brain metastases (BrMs) originating from lung cancer (LC), breast cancer (BC), ovarian cancer (OC), and colorectal cancer (CC)...

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases with atypical manifestations. The aim of this study was to utilize urine metabolomics to explore potential biomarkers for the diagnosis and prognosis of CSDH. METHODS: Seventy-seven healthy controls and ninety-two patients with CSDH were enrolled in our study. In total, 261 urine samples divided into the discovery group and validation group were analyzed by LC-MS. The statistical analysis and functional annotation were applied to discover potential biomarker panels and altered metabolic pathways...

PURPOSE: This research aimed to find potential HER2 mutations that would have an impact on breast cancer and investigate the underlying mechanism. EXPERIMENTAL DESIGN: This study first investigated 238 pairs of breast cancer and para-cancerous tissue samples from patients on the targeted next-generation sequencing (tNGS) platform. CCK-8 and clone formation assay were used to investigate whether the mutation exerts proliferative effects on breast cancer cells. In addition, mass spectrometry-based comparative proteomic and phosphoproteomic analyses of the mutation types and wild types of MCF-7 cell lines were carried out...

PURPOSE: Elevated levels of inflammation associated with human immunodeficiency virus (HIV) infection are one of the primary causes for the burden of age-related diseases among people with HIV (PWH). Circulating proteins can be used to investigate pathways to inflammation among PWH. EXPERIMENTAL DESIGN: We profiled 73 inflammation-related protein markers and assessed their associations with chronological age, sex, and CD4+ cell count among 87 black South African PWH before antiretroviral therapy (ART)...

PURPOSE: Plasma is an abundant source of protein biomarkers. Mass spectrometry (MS) is an effective means to measure a large number of proteins in a single run. The recent development of data-independent acquisition with parallel accumulation and serial fragmentation (diaPASEF) on a trapped ion mobility spectrometer (TIMS) affords deep proteomic coverage with short liquid chromatography gradients. In this work, we utilized a process optimization approach, design of experiments (DoE), to maximize precursor identification for a plasma proteomic diaPASEF workflow...

Alzheimer's disease (AD), one of the most common dementias, is a neurodegenerative disease characterized by cognitive impairment and decreased judgment function. The expected number of AD patient is increasing in the context of the world's advancing medical care and increasing human life expectancy. Since current molecular mechanism studies on AD pathogenesis are incomplete, there is no specific and effective therapeutic agent. Mass spectrometry (MS)-based unbiased proteomics studies provide an effective and comprehensive approach...

PURPOSE: The SARS-CoV-2 pandemic prompted the development and use of next-generation vaccines. Among these, mRNA-based vaccines consist of injectable solutions of mRNA encoding for a recombinant Spike, which is distinguishable from the wild-type protein due to specific amino acid variations introduced to maintain the protein in a prefused state. This work presents a proteomic approach to reveal the presence of recombinant Spike protein in vaccinated subjects regardless of antibody titer...

PURPOSE: Urine proteome is a valuable reservoir of biomarkers for disease diagnosis and monitoring. Following formation as the plasma filtrate in the kidney, urine is progressively modified by the active reabsorption and secretion of the urinary tract. However, little is known about how the urine proteome changes as it passes along the urinary tract. EXPERIMENTAL DESIGN: To investigate this, we compared the proteome composition of the renal pelvis urine (RPU) and individually self-voided bladder urine (BU) collected from seven unilateral urinary tract obstruction male patients by LC-MS/MS screening...

PURPOSE: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. EXPERIMENTAL DESIGN: CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0...

PURPOSE: Brucella canis is pathogenic for dogs and humans. Serological diagnosis is a cost-effective approach for disease surveillance, but a major drawback of current serological tests is the cross-reactivity with other bacteria that results in false positive reactions. Development of indirect tests with improved sensitivity and specificity that use selected B. canis proteins instead of the whole antigen remain a priority. EXPERIMENTAL DESIGN: A western blotting assay was developed to define the serum antibody patterns associated to infection using a panel of positive and negative dog sera...

PURPOSE: Stroke is the sudden death of brain cells in a localized area due to an inadequate blood flow or blood vessel rupture, and it seriously affects the quality of life. The metabolite biomarkers are needed for predicting the functional outcome of acute ischemic stroke (AIS). EXPERIMENTAL DESIGN: To identify biomarkers for AIS, untargeted LC/MS metabolomics was performed on plasma samples from subjects with favorable prognosis (mRS ≤ 2) and unfavorable prognosis (mRS > 2)...

INTRODUCTION: Kidney transplant recipients (KTRs) are at an increased risk of fractures. Total urinary hydroxyproline excretion served as marker for bone resorption (BR) but was replaced by β-CrossLaps (CTX), a C-terminal collagen α-1(I) chain (COL1A1) telopeptide. We investigated the low-molecular-weight urinary proteome for peptides associated with changes in bone metabolism after kidney transplantation. METHODS: Clinical and laboratory data including serum levels of CTX in 96 KTR from two nephrology centers were correlated with signal intensities of urinary peptides identified by capillary electrophoresis mass spectrometry...

PURPOSE: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression. EXPERIMENTAL DESIGN: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses. RESULTS: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes...

PURPOSE: The endoplasmic reticulum (ER) is the major site of protein synthesis and folding in the cell. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the main mechanisms of ER-mediated cell stress adaptation. Targeting the cell stress response is a promising therapeutic approach in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: Protein expression levels of valosin-containing protein (VCP), a chief element of ERAD, were measured in peripheral blood samples from in 483 pediatric AML patients using reverse phase protein array methodology...

Breast cancer, a multi-networking heterogeneous disease, has emerged as a serious impediment to progress in clinical oncology. Although technological advancements and emerging cancer research studies have mitigated breast cancer lethality, a precision cancer-oriented solution has not been achieved. Thus, this review will persuade the acquiescence of proteomics-based diagnostic and therapeutic options in breast cancer management. Recently, the evidence of breast cancer health surveillance through imaging proteomics, single-cell proteomics, interactomics, and post-translational modification (PTM) tracking, to construct proteome maps and proteotyping for stage-specific and sample-specific cancer subtyping have outperformed conventional ways of dealing with breast cancer by increasing diagnostic efficiency, prognostic value, and predictive response...

PURPOSE: This study aimed to identify serum glycoprotein biomarkers for early detection of high-grade serous ovarian cancer (HGSOC), the most common and aggressive histotype of ovarian cancer. EXPERIMENTAL DESIGN: The glycoproteomics pipeline lectin magnetic bead array (LeMBA)-mass spectrometry (MS) was used in age-matched case-control serum samples. Clinical samples collected at diagnosis were divided into discovery (n = 30) and validation (n = 98) sets...

PURPOSE: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and poor prognosis. Saliva is an important source for discovering biomarkers and contains an abundance of biological information. The purpose of this study was to determine whether galactosylation levels of salivary proteins are associated with LC. EXPERIMENTAL DESIGN: First, we analyzed the alterations of the glycopatterns recognized by Bandeiraea Simplicifolia Lectin I (BS-I) in five groups (healthy volunteers [HV]: 28, benign pulmonary disease [BPD]: 27, lung adenocarcinoma [ADC]: 39, squamous cell carcinoma [SCC]: 28, small-cell lung cancer [SCLC]: 22) of 144 saliva samples using lectin microarrays...

Prostate cancer (PCa) is the most prevalent malignancy of the male genitourinary system, and its etiology suggests that genetics is an essential risk factor for its development and progression, while exogenous factors may have an significant impact on this risk. Initial diagnosis of advanced prostate cancer is relatively frequent, and androgen deprivation therapy (ADT) is the predominant standard of care for PCa and the basis for various novel combination therapy regimens, and is often required throughout the patient's subsequent treatment...

PURPOSE: Helcococcus kunzii is a skin commensal, Gram-positive bacterium, mostly isolated from infected chronic wounds. This opportunistic pathogen is usually co-isolated with Staphylococcus aureus. The present dataset explores the production and secretion of H. kunzii bacterial virulence interacting proteins in a growth medium mimicking chronic wounds in exponential and stationary growth phases. EXPERIMENTAL DESIGN: The H. kunzii cellular proteome and exoproteome were assessed by analyzing three biological replicates per condition tested...

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The occurrence and development of HCC are closely related to epigenetic modifications. Epigenetic modifications can regulate gene expression and related functions through DNA methylation. This paper presents an association analysis method of HCC-related hub proteins and hub genes. EXPERIMENTAL DESIGN: Bioinformatics analysis of HCC-related DNA methylation data is carried out to clarify the molecular mechanism of HCC-related genes and to find hub genes (genes with more connections in the network) by constructing in the gene interaction network...