Glucose-6-Phosphate Dehydrogenase as a Prognostic Predictor Correlates with the Tumor Immune Activity Including Programmed Death Ligand-1 Expression in Merkel Cell Carcinoma
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ABSTRACT:
PROVIDER: PRJNA647905 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12300057_1.fastq.gz | Fastqsanger.gz | |||
| SRR12300057_2.fastq.gz | Fastqsanger.gz | |||
| SRR12300058_1.fastq.gz | Fastqsanger.gz | |||
| SRR12300058_2.fastq.gz | Fastqsanger.gz | |||
| SRR12300059_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Merkel cell carcinoma (MCC) is a rare but highly malignant skin cancer. However, it is well known that some cases have a good prognosis including spontaneously regression. To precise such a different patient’s outcome, reported prognostic markers, e.g. Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, are still insufficient. Here we performed RNA sequencing to evaluate immune response and comprehensively estimate prognostic values of immunogenic factors in MCC. Experimental Design: We collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC from 9 facilities. mRNA was extracted from formalin fixed paraffin embedded (FFPE) tissues. Analyses of next generation sequencing data, immunohistochemical staining and blood serum tests were performed. Results: Next generation sequencing revealed that MCC samples could be divided into two types. “immune active type” showed better clinical outcomes than “cell division type”. Glucose-6-Phosphate Dehydrogenase (G6PD) was one of the most significantly up-regulated gene in “cell division type”. G6PD expression correlated with the presence or absence of lymph node or distant metastases during the course and negatively correlated with high or low of PD-L1 expression with the top significance in 395 genes both. Immunohistochemical staining of G6PD was also correlated with disease specific survival and showed less heterogeneity compared with PD-L1 expression. G6PD activity was measurable by the blood serum test and detection values significantly increased as the cancer stage progression and significantly decreased after treatment. Conclusion: G6PD expression was an immunohistochemically and serum-detectable prognostic marker and negatively correlated with immune activity including PD-L1 associate with the prediction of immunotherapy response.
2020-12-13 | GSE154938 | GEO
Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCV+ Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and down-regulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. Two-conditions experiment, MCV vs Normal Merkel Cell. Biological replicates : 4 MCV (Cy5), 1 control = pool of Normal Merkel cells from 3 liftings
2014-01-01 | E-GEOD-50434 | biostudies-arrayexpress
Project description:Merkel cell carcinoma is supposed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly known events. A transcriptional profiling with cDNA microarrays was performed on cells from MCPyV(+) Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and downregulated genes. The extensive list of genes identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy.
2014-01-01 | GSE50434 | GEO
Project description:Merkel cells are epidermal mechanoreceptor cells responsible for the perception of gentle touch. Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer. Although MCC histologically resembles Merkel cells, the cell of origin for MCC is unknown. MCC frequently contains integrated Merkel cell polyomavirus (MCPyV), a small DNA tumor virus with widespread prevalence. Whether MCPyV can transform Merkel cells is unknown. Here, we describe the isolation and long-term expansion of human Merkel cells from neonatal foreskin. We validated the expression of several Merkel cell-related factors by RNASeq, and assessed the ultrastructure by electron microscopy. Culture of Merkel cell preparations on an artificial basement membrane promoted the formation of structures containing both Merkel and non-Merkel cell populations. To determine whether Merkel cells were susceptible to transformation, we expressed tumor-derived MCPyV T antigens and additional oncogenes. We were unable to demonstrate tumorigenesis in immunodeficient mice, but were able to detect T antigen expression from excised cells weeks after implantation. These results highlight that foreskin-isolated Merkel cells can be propagated extensively, sustain expression of MCPyV T antigens, but are not susceptible to transformation by MCPyV, suggesting that Merkel cells from non-glabrous skin may not be a cell of origin for MCC.
2017-04-01 | GSE79657 | GEO
Project description:BackgroundMerkel cell carcinoma (MCC) is a rare and highly malignant skin cancer. Some cases have a good prognosis and spontaneous regression can occur. Reported prognostic markers, such as Merkel cell polyoma virus infection or programmed death ligand-1 (PD-L1) expression, remain insufficient for precisely estimating the vastly different patient outcomes. We performed RNA sequencing to evaluate the immune response and comprehensively estimate prognostic values of immunogenic factors in patients with MCC.MethodsWe collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC at 10 facilities. The mRNA was extracted from formalin-fixed paraffin-embedded tissues. Next-generation sequencing, immunohistochemical staining and blood serum tests were performed.ResultsNext-generation sequencing results classified MCC samples into two types: the 'immune active type' was associated with better clinical outcomes than the 'cell division type'. Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene was highly significantly upregulated in the 'cell division type'. Among 395 genes, G6PD expression correlated with the presence of lymph node or distant metastases during the disease course and significantly negatively correlated with PD-L1 expression. Immunohistochemical staining of G6PD also correlated with disease-specific survival and exhibited less heterogeneity compared with PD-L1 expression. G6PD activity could be measured by a blood serum test. The detection values significantly increased as the cancer stage progressed and significantly decreased after treatment.ConclusionsG6PD expression was an immunohistochemically and serum-detectable prognostic marker that negatively correlated with immune activity and PD-L1 levels, and could be used to predict the immunotherapy response.
| S-EPMC7759960 | biostudies-literature
Project description:We performed miRNA expression profiling in a series of human Merkel Cell carcinoma samples using a microarray approach. Significant differentially expressed miRNAs among groups were identified using SAM analysis. Agilent microarray platform containing 723 human miRNAs was used to determine miRNA expression profiles in 16 human Merkel cell carcinoma (MCC) samples. To validate the microarray platform, the expression levels of selected miRNAs were evaluated using qRT-PCR.
2013-12-31 | E-GEOD-43699 | biostudies-arrayexpress
Project description:We describe Merkel cell formation in glabrous skin during embryogenesis. In our study, we first found that Merkel cells were specified at E15.5, 24 hours later, comparing to the back skin. Interestingly, by performing lineage-tracing experiments, we found that unlike back skin, SOX9(+) cells do not give rise to Merkel cells in glabrous skin. We performed transcriptional profiling of Merkel cells of the back and glabrous skin and showed that their transcriptoms are very similar. Taken together, Merkel cells in back skin and glabrous skin are similar, and their formation is controlled by a common genetic program, although their precursor cells might differ.
2021-11-14 | GSE122598 | GEO
Project description:Array-CGH profiles of Merkel cell carcinoma tumors Experiment Overall Design: We perfromed array-CGH on 25 Merkel cell carcinoma tumor samples (2 primary/metastasis pairs) looking for recurrent gains/losses among the cohort of tumors. Experiment Overall Design: Results from the Analysis of Copy Errors (ACE) may be found in GSE13239_MccACEAnalyzedData.txt. Experiment Overall Design: The overall profiles of the primary/metastasis pairs are similar. These metastases samples, 1m and 3m, were excluded from the ACE analysis.
2009-01-14 | E-GEOD-13239 | biostudies-arrayexpress
Project description:Array-CGH profiles of Merkel cell carcinoma tumors Keywords: fresh frozen and formalin fixed paraffin embedded primary tumor, nodal and metastasis merkel cell carcinoma tumor samples
2009-01-01 | GSE13239 | GEO
Project description:Epithelial-neuronal signaling is essential for sensory encoding in touch, itch and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as framework to directly test this hypothesis. RNA sequencing of adult Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogues. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of b2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch.
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