RESUMO
PURPOSE: There are no blood biomarkers to detect early-stage oral cavity squamous cell carcinoma (OSCC) prior to clinical signs. Most OSCC incidence is associated with significant morbidity and poor survival. The authors aimed to use mass-spectrometry (MS) technology to find specific N-glycopeptides potentially serving as serum biomarkers for preclinical OSCC screening. EXPERIMENTAL DESIGN: Serum samples from 14 patients treated for OSCC (stage I or stage IV) with 12 age- and sex-matched controls are collected. Quantitative label-free N-glycoproteomics is performed, with MS/MS analysis of the statistically significantly different N-glycopeptides. RESULTS: Combined with a database search using web-based software (GlycopeptideID), MS/MS provided detailed N-glycopeptide information, including glycosylation site, glycan composition, and proposed structures. Thirty-eight tryptic N-glycopeptides are identified, having 19 unique N-glycosylation sites representing 14 glycoproteins. OSCC patients, including stage I tumors, can be differentiated from healthy controls based on the expression levels of these glycoforms. N-glycopeptides of IgG1, IgG4, haptoglobin, and transferrin have statistically significant different abundances between cases and controls. CONCLUSIONS AND CLINICAL RELEVANCE: The authors are the first to suggest specific N-glycopeptides to serve as potential serum biomarkers to detect preclinical OSCC in patients. These N-glycopeptides are the lead candidates for validation as future diagnostic modalities of OSCC as early as stage I.
Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , Glicopeptídeos/sangue , Neoplasias da Língua/sangue , Adulto , Idoso , Feminino , Glicosilação , Haptoglobinas/metabolismo , Voluntários Saudáveis , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polissacarídeos/química , Isomerases de Dissulfetos de Proteínas/sangue , Transferrina/metabolismoRESUMO
Bloodstream infections are associated with high morbidity and mortality with rates varying from 10-25% and higher. Appropriate and timely onset of antibiotic therapy influences the prognosis of these patients. It requires the diagnostic accuracy which is not afforded by current gold standards such as blood culture. Moreover, the time from blood sampling to blood culture results is a key determinant of reducing mortality. No established biomarkers exist which can differentiate bloodstream infections from other systemic inflammatory conditions. This calls for studies on biomarkers potential of molecular profiling of plasma as it is affected most by the molecular changes accompanying bloodstream infections. N-glycosylation is a post-translational modification which is very sensitive to changes in physiology. Here we have performed targeted quantitative N-glycoproteomics from plasma samples of patients with confirmed positive blood culture together with age and sex matched febrile controls with negative blood culture reports. Three hundred and sixty eight potential N-glycopeptides were quantified by mass spectrometry and 149 were further selected for identification. Twenty four N-glycopeptides were identified with high confidence together with elucidation of the peptide sequence, N-glycosylation site, glycan composition and proposed glycan structures. Principal component analysis, orthogonal projections to latent structures-discriminant analysis (S-Plot) and self-organizing maps clustering among other statistical methods were employed to analyze the data. These methods gave us clear separation of the two patient classes. We propose high-confidence N-glycopeptides which have the power to separate the bloodstream infections from blood culture negative febrile patients and shed light on host response during bacteremia. Data are available via ProteomeXchange with identifier PXD009048.
Assuntos
Bacteriemia/sangue , Bacteriemia/metabolismo , Proteínas Sanguíneas/metabolismo , Glicopeptídeos/metabolismo , Proteômica , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicopeptídeos/sangue , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Processamento de Proteína Pós-TraducionalRESUMO
Orogastric tube (OGT) procedures are done in 20% of newborn unit cases. This study was contemplated to work out a formula to predict OGT length in terms of femur length in neonates and its agreement to existing standards. In this observational study, OGT length was estimated using NEMU (nose-ear-mid umbilicus) in 53 consecutive newborns. Their anterior superior iliac spine to tibial tuberosity length (AS-TT) was measured and equated using linear regression analysis in Stata. We further verified the accuracy of the new formula and comparison of time taken by both the methods. Strong positive correlation was seen between OGT and AS-TT (r = .88). OGT length was 10.14 + 0.88 AS-TT, which can be used in neonatal intensive care unit newborns with greater accuracy and with lesser time than the classical method. Strong agreement levels were seen. AS-TT closely relates to the femur length and can be chosen as a guide as it is faster when compared to other methods.