Abstract:Keratins (KRTs), the intermediate filament-forming proteins of epithelial cells, are extensively used as diagnostic biomarkers in cancers and associated with tumorigenesis and metastasis in multiple cancers. However, the diverse expression patterns and prognostic values of KRTs in melanoma have yet to be elucidated. In the current study, we examined the transcriptional and clinical data of KRTs in patients with melanoma from GEO, TCGA, ONCOMINE, GEPIA, cBioPortal, TIMER and TISIDB databases. We found that the … Show more
“…4 D). These results are consistent with the literature [ 21 – 26 ], clearly demonstrate the validity of IMC, and support the application of the method in ocular research and diagnostics. Fig.…”
Background
Imaging mass cytometry (IMC) combines the principles of flow cytometry and mass spectrometry (MS) with laser scanning spatial resolution and offers unique advantages for the analysis of tissue samples in unprecedented detail. In contrast to conventional immunohistochemistry, which is limited in its application by the number of possible fluorochrome combinations, IMC uses isoptope-coupled antibodies that allow multiplex analysis of up to 40 markers in the same tissue section simultaneously.
Methods
In this report we use IMC to analyze formalin-fixed, paraffin-embedded conjunctival tissue. We performed a 18-biomarkers IMC analysis of conjunctival tissue to determine and summarize the possibilities, relevance and limitations of IMC for deciphering the biology and pathology of ocular diseases.
Results
Without modifying the manufacturer’s protocol, we observed positive and plausible staining for 12 of 18 biomarkers. Subsequent bioinformatical single-cell analysis and phenograph clustering identified 24 different cellular clusters with distinct expression profiles with respect to the markers used.
Conclusions
IMC enables highly multiplexed imaging of ocular samples at subcellular resolution. IMC is an innovative and feasible method, providing new insights into ocular disease pathogenesis that will be valuable for basic research, drug discovery and clinical diagnostics.
“…4 D). These results are consistent with the literature [ 21 – 26 ], clearly demonstrate the validity of IMC, and support the application of the method in ocular research and diagnostics. Fig.…”
Background
Imaging mass cytometry (IMC) combines the principles of flow cytometry and mass spectrometry (MS) with laser scanning spatial resolution and offers unique advantages for the analysis of tissue samples in unprecedented detail. In contrast to conventional immunohistochemistry, which is limited in its application by the number of possible fluorochrome combinations, IMC uses isoptope-coupled antibodies that allow multiplex analysis of up to 40 markers in the same tissue section simultaneously.
Methods
In this report we use IMC to analyze formalin-fixed, paraffin-embedded conjunctival tissue. We performed a 18-biomarkers IMC analysis of conjunctival tissue to determine and summarize the possibilities, relevance and limitations of IMC for deciphering the biology and pathology of ocular diseases.
Results
Without modifying the manufacturer’s protocol, we observed positive and plausible staining for 12 of 18 biomarkers. Subsequent bioinformatical single-cell analysis and phenograph clustering identified 24 different cellular clusters with distinct expression profiles with respect to the markers used.
Conclusions
IMC enables highly multiplexed imaging of ocular samples at subcellular resolution. IMC is an innovative and feasible method, providing new insights into ocular disease pathogenesis that will be valuable for basic research, drug discovery and clinical diagnostics.
“…Keratins (KRTs) are a family of intermediate filament proteins that are responsible for the structural integrity of epithelial cells and play significant roles in the occurrence, progression, and metastasis of multiple cancers [ 45 ]. KRT8 and KRT19 are two oncogenes important in development of human cancers, with high expression and hypomethylated promoters [ 29 ].…”
Section: Epigenetic Regulation Of Emt Biomarkersmentioning
Epithelial to mesenchymal transition (EMT) occurs during the pathological process associated with tumor progression and is considered to influence and promote the metastatic cascade. Characterized by loss of cell adhesion and apex base polarity, EMT enhances cell motility and metastasis. The key markers of the epithelial to mesenchymal transition are proteins characteristic of the epithelial phenotype, e.g., E-cadherin, cytokeratins, occludin, or desmoplakin, the concentration and activity of which are reduced during this process. On the other hand, as a result of acquiring the characteristics of mesenchymal cells, an increased amount of N-cadherin, vimentin, fibronectin, or vitronectin is observed. Importantly, epithelial cells undergo partial EMT where some of the cells show both epithelial and mesenchymal characteristics. The significant influence of epigenetic regulatory mechanisms is observed in the gene expression involved in EMT. Among the epigenetic modifications accompanying incorrect genetic reprogramming in cancer are changes in the level of DNA methylation within the CpG islands and posttranslational covalent changes of histone proteins. All observed modifications, which are stable but reversible changes, affect the level of gene expression leading to the development and progression of the disease, and consequently affect the uncontrolled growth of the population of cancer cells.
“…Besides, the 16 DEGs between preinvasive and invasive lesions (Figure 2F) demonstrated good performance in discriminating CIN from cervical cancer in our test data. The four up-regulated genes, including CD74, MT2A, KRT5, and KRT15, were associated with tumor progression in several types of squamous cell carcinomas [57][58][59][60] , their prognostic values in CSCC may worth further investigations.…”
To understand the etiological, structural, and immunological characteristics of cervical squamous cell carcinoma (CSCC), we conducted single nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (ST) experiments for cervical samples from 20 individuals. When exploring the possible factors shaping the intra-individual immune heterogeneity in CSCC, we identified a cluster of cancer-associated fibroblasts (CAFs) enriched around some tumors, which highly expressed ACTA2, POSTN, ITGB4, and FAP. Results showed that the CAFs might support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling the tumor extracellular matrix. Moreover, high CAF signals predicted poorer clinical outcomes for CSCC patients. Our data also revealed the infection profiles of HPV in tumors, the critical factors involved in the progression of cervical cancerous lesions, and the association between tumor metabolism and immune response intensity. Collectively, our findings may improve the prognostic and therapeutic methods for CSCC.
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