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Biology subjects

Kowalski, L. P.

Publications and source records attributed to Kowalski, L. P..

4 recordsLinked to original sources

Single-cell proteomics maps circulating monocyte dynamics in advanced head and neck squamous cell carcinoma

It remains unclear whether metastatic progression in head and neck squamous cell carcinoma (HNSCC) is accompanied by functional remodeling of circulating immune cells at the proteome level. To address this question, we applied single-cell proteomics (SCP) to cryopreserved peripheral blood mononuclear cells (PBMCs) from three patients with HNSCC representing distinct stages of metastatic progression and two healthy donors. Proteomic analysis of 619 individual PBMCs resolved major immune cell populations, with up to 1,638 proteins quantified per cell. Trajectory inference, clustering, and differential abundance analyses revealed proteomic remodeling associated with disease progression, with the most pronounced changes occurring within a monocyte cluster composed exclusively of cells from patients with nodal metastasis. This population showed increased abundance of interferon-related proteins, HLA molecules, and myeloid immunoregulatory signatures, consistent with an activated, interferon-associated monocyte state. In parallel, lymphocytes showed reduced coordinated abundance of proteins associated with activation, cytotoxicity, and degranulation, consistent with altered cytotoxic effector programs across disease stages. Overall, these findings reveal distinct proteomic states in circulating monocytes and lymphocytes associated with HNSCC progression and identify selective remodeling of the monocyte compartment in nodal metastatic disease.

cancer biology↗

Tear fluid as noninvasive liquid biopsy reveals proteins associated with malignant transformation of oral lesions

Oral leukoplakias (OLs) are premalignant lesions that can progress into oral squamous cell carcinoma (OSCC). This study hypothesized that tear fluid, as a noninvasive biofluid, reflects proteomic alterations associated with malignant transformation. The tear proteome of 44 individuals, including healthy controls, OL/PVL (proliferative verrucous leukoplakia), and OSCC patients, was deeply profiled, revealing 828 protein groups clustered according to histopathological alterations. N-glycoproteome analysis identified immune-related proteins, while public RNA-seq integration indicated immune imbalance marked by increased B-cell and decreased macrophage signatures during disease progression. Several immune-associated proteins and epithelial markers, including desmoplakin, KRT14, and DSC1, emerged as potential indicators of malignant transformation. These findings demonstrate that tear fluid reflects oral carcinogenic processes, thereby serving as a noninvasive liquid biopsy for early detection and clinical monitoring.

biochemistry↗

Comprehensive glycoprofiling of oral tumours associates N-glycosylation with lymph node metastasis and patient survival

While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), its heterogeneous glycoproteome and dynamics with disease progression remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a valuable cohort of resected tumour tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumour tissues displayed uniform N-glycome profiles suggesting relatively stable global N-glycosylation during lymph node metastasis, glycoproteomics and advanced correlation analysis notably uncovered altered site-specific N-glycosylation and previously unknown associations with several key clinicopathological features. Importantly, focused analyses of the multi-omics data unveiled two N-glycans and three N-glycopeptides that were closely associated with patient survival. This study provides novel insight into the complex OSCC tissue N-glycoproteome forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glyco-markers for OSCC. TeaserDeep survey of the dynamic landscape of complex sugars in oral tumours paves a way for new prognostic disease markers.

cancer biology↗

Wiring multiple microenvironment proteomes uncovers the biology in head and neck cancer

The poor prognosis of head and neck cancer (HNC) is associated with the presence of metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identified a nodal metastasis signature in the blood and saliva. In summary, we present the deepest proteome characterization wiring multiple sampling sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

cancer biology↗