Fast NMR-Based Assessment of Cancer-Associated Protein Glycosylations from Serum Samples

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Nuclear magnetic resonance (NMR) spectra of blood serum and plasma show signals arising from metabolites, lipoproteins, N-acetyl methyl groups N-glycans covalently linked to acute-phase proteins. These glycan often called glycoprotein A (GlycA) B (GlycB) arise have been proposed as biomarkers, initially for cardiovascular diseases, but also other inflammatory conditions. For the detection resonances, J-edited, diffusion, relaxation filtered NMR spectroscopy (JEDI) has suppress lipoprotein signals. JEDI is however limited measure those acetyl signals, whereas all cannot be observed. improved profiling, pyranose ring protons are essential. Here, we how selective frequency excitation combined with scalar coupling filtering can used dramatically increase number N-glycan observable in samples, facilitating glycosylation profiling less than 30 min. This approach grants sialylation, galactosylation, N-acetylglucosaminylation, fucosylation dominant and, some extent, branching complexity. Notably, sialylated nonsialylated Lewisx Lewisa antigens antigen well established a cancer biomarker, known CA19-9. profiles nine isolated glycoproteins excellent agreement well-established UHPLC-MS analysis. The method facilitates biomarkers without need enzymatic treatment or provides robust read-out exemplified by samples 33 patients hepatocellular carcinoma.

Language: Английский

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HEXB drives raised paucimannosylation in colorectal cancer and stratifies patient risk

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100927 - 100927

Published: Feb. 1, 2025

Highlights•Multi-omics investigation of colorectal cancer specimens (tissues, PBMCs, plasma).•Paucimannosidic proteins immune and origins dominate in CRC tumors.•HEXB, a truncating glycoenzyme, drives paucimannosidic protein formation CRC.•Plasma hexosaminidase activity associates with five-year survival patients.AbstractNon-invasive prognostic markers are needed to improve the (CRC) patients. Towards this goal, we applied untargeted systems glycobiology approaches snap frozen formalin-fixed paraffin-embedded tumor tissues peripheral blood mononuclear cells (PBMCs) from patients spanning different disease stages matching controls faithfully uncover molecular changes associated CRC. Quantitative glycomics immunohistochemistry (IHC) revealed that non-canonical N-glycans elevated tumors relative normal adjacent tissues. Cell origin-focused glycoproteomics enabled using well-curated Human Protein Atlas combined IHC recapitulated these findings indicated were part tumor-infiltrating monocytes (e.g. MPO, AZU1) cell origin LGALS3BP, PSAP). Biosynthetically explaining observations, N-acetyl-β-D-hexosaminidase (Hex) subunit β (HEXB) was found be over-expressed colocalization enzyme inhibition studies confirmed HEXB facilitates biosynthesis cells. Employing sensitive, quick robust assay, then showed Hex plasma PBMCs advanced those early-stage disease. Surveying large cohort, raised correlated indicating is potential risk marker for patient outcome. Our glycoproteomics-driven open avenues better prognostication stratification CRC.Graphical abstract

Language: Английский

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Construction of electrochemical immunosensor by integrating N, S doped carbon dots with Fe2O3 for ultrasensitive sensing alpha-fetoprotein

Talanta, Journal Year: 2025, Volume and Issue: 291, P. 127887 - 127887

Published: March 3, 2025

Language: Английский

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Target-Triggered Enzymatic Cascade LF-NMR Biosensor for the Detection of Circulating Tumor Cells

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

A target-triggered, enzymatic cascade-amplified low-field nuclear magnetic resonance (LF-NMR) sensor was developed for the detection of circulating tumor cell (CTC) A549. multifunctional two-dimensional bionanomaterial GDA@GOX&DNA1 designed as initiator, with Fe3O4@DNA2/Apt recognition unit and CaO2@MnO2 signal unit. When A549 present, aptamer (Apt) detached from unit, allowing formation GDA@GOX&DNA1-DNA2@Fe3O4 triggering following reactions: (1) glucose oxidase (GOX) catalyzed reaction between substrate oxygen (O2) to produce gluconic acid hydrogen peroxide (H2O2); (2) generated H2O2 reacted MnO2, producing probes Mn2+ O2; (3) CaO2 acid, generating H2O2. These cyclic reactions brought generation massive a decrease transverse relaxation time (T2), resulting in LF-NMR biosensing CTCs. Under optimal experimental conditions, linear range limit (LOD) were 10–1.0 × 106 6 cells/mL, respectively. The feasibility reliability practical applications verified by using spiked whole blood samples containing cells. This study represents first successful demonstration an biosensor intact CTCs, providing new tool clinical testing diagnosis.

Language: Английский

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Pan-cancer analysis of the prognosis and immune infiltration of NSUN7 and its potential function in renal clear cell carcinoma

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 18, 2025

NSUN7, an enzyme responsible for the RNA m5c modification, has been recognized as a valuable indicator predicting and diagnosing array of cancer. Nevertheless, there is still scarcity thorough analyses exploring its diagnostic, predictive, immune system-related importance in various types We integrated multiple publicly available databases, including TCGA, TISIDB, TISCH2, UALCAN, to comprehensively investigate role NSUN7 pan-cancer across omics data types. The research included examining survival rates, genetic mutations, cell presence tumors, analyzing differences gene expression, studying individual cells, among other things. expression showed increase 12 cancer decrease another was discovered be linked with enhanced rates bladder urothelial carcinoma (BLCA), kidney renal clear (KIRC), papillary (KIRP), lung adenocarcinoma (LUAD), pheochromocytoma paraganglioma (PCPG), skin cutaneous melanoma (SKCM), uveal (UVM).On hand, seemed have detrimental impact on prognosis glioblastoma multiforme/brain lower grade glioma (GBMLGG), adrenocortical (ACC),acute myeloid leukemia (LAML), stomach (STAD), brain (LGG). Furthermore, our experimental validation confirmed inhibitory effect proliferation while elucidating specific part blocking cycle progression. findings underscore potential utility prognostic patients offer insights into mechanisms underlying initiation

Language: Английский

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Improved breast cancer diagnosis using a CA15-3 capture antibody-lectin sandwich assay

Breast Cancer Research and Treatment, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

This study aims to test the hypothesis that an enzyme-linked antibody-lectin sandwich assay for a glycovariant of CA15-3 can deliver better diagnostic performance, defined by classification accuracy, sensitivity and specificity, breast cancer compared existing FDA-approved test. A genetically engineered lectin (SubB2M) specifically binds N-glycolylneuraminic acid (Neu5Gc) was used as detection reagent in capture (neuCA15-3) assay. In case: control cohort equivalence accuracy neuCA15-3 determined IVD (Elecsys II, Roche Diagnostics). Classification AUC were 81% 0.886 ± 0.015 (standard error, n = 567) Elecsys 55% 0.642 0.023 (n 558), respectively. At threshold cut-off serum concentration 23.6 units/ml, overall (compared comparator assay, p < 0.001). 95% 69.5%, significantly greater than (11.9%, concentrations did not vary with receptor subtype or comorbidities tested. The performance substantially improved targeting both protein epitope pan-cancer glycan (the specific binding target SubB2M). reporter signal generated depends on colocalization antigen aberrant sialylation protein, thus increasing specificity. presence multiple Neu5Gc lectin-binding sites per glycoprotein molecule increases generation sensitivity. inclusion additional biomarkers multivariate index format may further increase cancer.

Language: Английский

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sEV-mediated intercellular transformation from MGAT4AHigh to MGAT4ALow tumor cells via the HOTAIRM1/miR-196b-5p axis promotes apoptosis resistance in CTCL

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

ncRNAs encapsulated in small extracellular vesicles (sEVs) facilitate intercellular communication and are associated with tumor progression. lncRNA-HOTAIRM1 is aberrantly expressed various cancers. However, HOTAIRM1 expression its downstream ceRNA network CTCL remains unclear. In this study, we found that was reduced CTCL. Elevated inhibited proliferation induced apoptosis vitro, resulting vivo tumorigenic capacity. Whole-transcriptome sequencing scRNA-Seq confirmed differential of HOTAIRM1/miR-196b-5p/MGAT4A axis induces resistance Mechanistically, MGAT4A leads to decreased N-glycosylation modification membrane proteins Galectin-1 affinity, thereby inducing partial Galectin-1-induced apoptosis. Meanwhile, benign CD4 + T cells show sensitivity due their relatively higher expression. Furthermore, MGAT4ALow transformed MGAT4AHigh CD4+ into by secreting sEVs containing miR-196b-5p, reducing binding resistance. Engineered from HOTAIRM1-overexpressing contain elevated HOTAIRM1, which can specifically target malignant cells, miR-196b-5p increased MGAT4A, demonstrating apoptosis-inducing tumor-suppressive effects This study identified changes modifications HOTAIRM1-loaded demonstrated promising targeting therapeutic

Language: Английский

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Evaluation of Blood- and Urine-Derived Biomarkers for Machine Learning Prediction Models of Osteoarthritis in Elderly Patients: A Feasibility Study

Computer Methods and Programs in Biomedicine, Journal Year: 2025, Volume and Issue: 266, P. 108779 - 108779

Published: April 14, 2025

Language: Английский

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Aberrant protein glycosylation in the colon adenoma-cancer sequence: Colorectal cancer mechanisms and clinical implications

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167853 - 167853

Published: April 1, 2025

Language: Английский

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Expression of 9-O-Acetylated Sialic Acid in HPV+ Oral Squamous Cell Carcinoma Cells

Life, Journal Year: 2025, Volume and Issue: 15(4), P. 663 - 663

Published: April 17, 2025

Oral squamous cell carcinoma (OSCC) is a common type of head and neck malignancy that represents significant global health issue. Sialylations are events in tumor transformation, proliferation, metastasis, immune evasion. Modifications sialylation can be detected by lectins, whose changes OSCC have been related to grade, invasion, metastasis. The presence 9-O-acetylated sialic acid (Neu5,9Ac2) cells its potential expression, modification, role unknown. This study aimed analyze the expression Neu5,9Ac2 using Macrobrachium rosenbergii lectin (MrL) recognizes this (Neu5Ac) residue also compare effect on SCC-152 line (CRL-3240, ATCC) immortalized keratinocytes (HaCaT) as control. We observed immunocytochemistry expressed more compared HaCaT cells; specificity MrL was confirmed after sialidase treatment which loss lectin’s recognition observed. electrophoretic profile similar between both types; however, Western blot showed differences glycoprotein patterns recognized for each type. increased proliferation cells, well integrity morphology colonies. Therefore, our results suggest glycosylated receptors could involved survival offers promising avenue developing diagnostic prognostic tools (tumor markers) against oral future.

Language: Английский

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