Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent respiratory symptoms and airflow restriction. It is usually manifested as airway and/or alveolar abnormalities caused by significant exposure to harmful particulates or gases. Objective: We aim to explore plasma metabolomic changes in the acute exacerbation stage of COPD (AECOPD) and stable stage of COPD (Stable COPD) to identify potential biomarkers for diagnosis or prognosis in clinical practice. Methods: Untargeted metabolomics and lipidomics analyses were performed to investigate dysregulated molecules in blood plasma of AECOPD patients (n=48) and Stable COPD (n=48), and a cohort of healthy people were included as a control group (n=48). Statistical analysis and bioinformatics analysis were performed to reveal dysregulated metabolites and perturbed metabolic pathways. SVM-based multivariate ROC analysis was used for candidate biomarker screening. Results: A total of 142 metabolites and 688 lipids were dysregulated in COPD patients. Pathway enrichment analysis showed that several metabolic pathways were perturbed after COPD onset. Several biomarker panels were proposed for diagnosis of COPD vs healthy control and AECOPD vs Stable COPD with AUC greater than 0.9. Conclusion: Numerous plasma metabolites and several metabolic pathways were detected relevant to COPD disease onset or progression. These metabolites may be considered as candidate biomarkers for diagnosis or prognosis of COPD. The perturbed pathways involved in COPD provide clues for further pathological mechanism studies of COPD.

The machine learning–aided serum lipidomics approach could be used to help early diagnosis of patients with PDAC.

Background Nonkeratinizing nasopharyngeal carcinoma (NK-NPC) has a strong association with Epstein-Barr virus (EBV) infection. The role of NK cells and the tumor cell evolutionary trajectory in NK-NPC remain unclear. In this study, we aim to investigate the function of NK cell and the evolutionary trajectory of tumor cells in NK-NPC by single-cell transcriptomic analysis, proteomics and immunohistochemistry. Methods NK-NPC (n = 3) and normal nasopharyngeal mucosa cases (n = 3) were collected for proteomic analysis. Single-cell transcriptomic data of NK-NPC (n = 10) and nasopharyngeal lymphatic hyperplasia (NLH, n = 3) were obtained from Gene Expression Omnibus (GSE162025 and GSE150825). Quality control, dimension reduction and clustering were based on Seurat software (v4.0.2) process and batch effects were removed by harmony (v0.1.1) software. Normal cells of nasopharyngeal mucosa and tumor cells of NK-NPC were identified using copykat software (v1.0.8). Cell-cell interactions were explored using CellChat software (v1.4.0). Tumor cell evolutionary trajectory analysis was performed using SCORPIUS software (v1.0.8). Protein and gene function enrichment analyses were performed using clusterProfiler software (v4.2.2). Results A total of 161 differentially expressed proteins were obtained between NK-NPC (n = 3) and normal nasopharyngeal mucosa (n = 3) by proteomics (log2 fold change > 0.5 and P value < 0.05). Most of proteins associated with the nature killer cell mediated cytotoxicity pathway were downregulated in the NK-NPC group. In single cell transcriptomics, we identified three NK cell subsets (NK1-3), among which NK cell exhaustion was identified in the NK3 subset with high ZNF683 expression (a signature of tissue-resident NK cell) in NK-NPC. We demonstrated the presence of this ZNF683 + NK cell subset in NK-NPC but not in NLH. We also performed immunohistochemical experiments with TIGIT and LAG3 to confirm NK cell exhaustion in NK-NPC. Moreover, the trajectory analysis revealed that the evolutionary trajectory of NK-NPC tumor cells was associated with the status of EBV infection (active or latent). The analysis of cell-cell interactions uncovered a complex network of cellular interactions in NK-NPC. Conclusions This study revealed that the NK cell exhaustion might be induced by upregulation of inhibitory receptors on the surface of NK cells in NK-NPC. Treatments for the reversal of NK cell exhaustion may be a promising strategy for NK-NPC. Meanwhile, we identified a unique evolutionary trajectory of tumor cells with active status of EBV-infection in NK-NPC for the first time. Our study may provide new immunotherapeutic targets and new sight of evolutionary trajectory involving tumor genesis, development and metastasis in NK-NPC.

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