Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

BACKGROUND: There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. METHODS: We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. RESULTS: We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. CONCLUSIONS: Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

Mass Spectrometry Analysis of Glycopeptides Enriched by Anion Exchange-Mediated Methods Reveals PolyLacNAc-Extended N-Glycans in Integrins and Tetraspanins in Melanoma Cells.

Glycosylation is a key modulator of the functional state of proteins. Recent developments in large-scale analysis of intact glycopeptides have enabled the identification of numerous glycan structures that are relevant in pathophysiological processes. However, one motif found in N-glycans, poly-N-acetyllactosamine (polyLacNAc), still poses a substantial challenge to mass spectrometry-based glycoproteomic analysis due to its relatively low abundance and large size. In this work, we developed approaches for the systematic mapping of polyLacNAc-elongated N-glycans in melanoma cells. We first evaluated five anion exchange-based matrices for enriching intact glycopeptides and selected two materials that provided better overall enrichment efficiency. We then tested the robustness of the methodology by quantifying polyLacNAc-containing glycopeptides as well as changes in protein fucosylation and sialylation. Finally, we applied the optimal enrichment methods to discover glycopeptides containing polyLacNAc motifs in melanoma cells and found that integrins and tetraspanins are substantially modified with these structures. This study demonstrates the feasibility of glycoproteomic approaches for identification of glycoproteins with polyLacNAc motifs.

Decoding the glycoproteome: a new frontier for biomarker discovery in cancer.

Cancer early detection and treatment response prediction continue to pose significant challenges. Cancer liquid biopsies focusing on detecting circulating tumor cells (CTCs) and DNA (ctDNA) have shown enormous potential due to their non-invasive nature and the implications in precision cancer management. Recently, liquid biopsy has been further expanded to profile glycoproteins, which are the products of post-translational modifications of proteins and play key roles in both normal and pathological processes, including cancers. The advancements in chemical and mass spectrometry-based technologies and artificial intelligence-based platforms have enabled extensive studies of cancer and organ-specific changes in glycans and glycoproteins through glycomics and glycoproteomics. Glycoproteomic analysis has emerged as a promising tool for biomarker discovery and development in early detection of cancers and prediction of treatment efficacy including response to immunotherapies. These biomarkers could play a crucial role in aiding in early intervention and personalized therapy decisions. In this review, we summarize the significant advance in cancer glycoproteomic biomarker studies and the promise and challenges in integration into clinical practice to improve cancer patient care.

Sirt3-Mediated Opa1 Deacetylation Protects Against Sepsis-Induced Acute Lung Injury by Inhibiting Alveolar Macrophage Pro-Inflammatory Polarization.

Aims: Mitochondrial dynamics in alveolar macrophages (AMs) are associated with sepsis-induced acute lung injury (ALI). In this study, we aimed to investigate whether changes in mitochondrial dynamics could alter the polarization of AMs in sepsis-induced ALI and to explore the regulatory mechanism of mitochondrial dynamics by focusing on sirtuin (SIRT)3-induced optic atrophy protein 1 (OPA1) deacetylation. Results: The AMs of sepsis-induced ALI showed imbalanced mitochondrial dynamics and polarization to the M1 macrophage phenotype. In sepsis, SIRT3 overexpression promotes mitochondrial dynamic equilibrium in AMs. However, 3-(1H-1, 2, 3-triazol-4-yl) pyridine (3TYP)-specific inhibition of SIRT3 increased the mitochondrial dynamic imbalance and pro-inflammatory polarization of AMs and further aggravated sepsis-induced ALI. OPA1 is directly bound to and deacetylated by SIRT3 in AMs. In AMs of sepsis-induced ALI, SIRT3 protein expression was decreased and OPA1 acetylation was increased. OPA1 acetylation at the lysine 792 amino acid residue (OPA1-K792) promotes self-cleavage and is associated with an imbalance in mitochondrial dynamics. However, decreased acetylation of OPA1-K792 reversed the pro-inflammatory polarization of AMs and protected the barrier function of alveolar epithelial cells in sepsis-induced ALI. Innovation: Our study revealed, for the first time, the regulation of mitochondrial dynamics and AM polarization by SIRT3-mediated deacetylation of OPA1 in sepsis-induced ALI, which may serve as an intervention target for precision therapy of the disease. Conclusions: Our data suggest that imbalanced mitochondrial dynamics promote pro-inflammatory polarization of AMs in sepsis-induced ALI and that deacetylation of OPA1 mediated by SIRT3 improves mitochondrial dynamic equilibrium, thereby ameliorating lung injury.

Study of Anticorrosion and Antifouling Properties of a Cu-Doped TiO2 Coating Fabricated via Micro-Arc Oxidation.

As a promising material for petroleum industrial applications, titanium (Ti) and its alloys receive wide attention due to their outstanding physicochemical properties. However, the harsh industrial environment requires an antifouling surface with a desired corrosion resistance for Ti and its alloys. In order to achieve the desired antifouling properties, micro-arc oxidation (MAO) was used to prepare a Cu-doped TiO2 coating. The microstructure of the Cu-doped TiO2 coating was investigated by TF-XRD, SEM, and other characterization techniques, and its antifouling and anticorrosion properties were also tested. The results show the effects of the incorporation of Cu (~1.73 wt.%) into TiO2 to form a Cu-doped TiO2, namely, a Ti-Cu coating. The porosity (~4.8%) and average pore size (~0.42 µm) of the Ti-Cu coating are smaller than the porosity (~5.6%) and average pore size (~0.66 µm) of Ti-blank coating. In addition, there is a significant reduction in the amount of SRB adhesion on the Ti-Cu coating compared to the Ti-blank coating under the same conditions, while there is little difference in corrosion resistance between the two coatings. There, the addition of copper helps to improve the fouling resistance of TiO2 coatings without compromising their corrosion resistance. Our work provides a practical method to improve the antifouling function of metallic Ti substrates, which could promote the application of Ti in the petroleum industry.