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Histopathological analysis of SGC of the eyelid. Hematoxylin and eosin staining of SGC (case 2) (a) and sebaceous adenoma (case 4) (b)
Source publication
Purpose
To investigate the overexpression of genes in sebaceous gland carcinoma (SGC) of the eyelid compared to sebaceous adenoma of the eyelid in order to elucidate the molecular mechanism underlying pathogenesis.
Methods
We performed histopathological examination of eyelid tissues surgically removed from four patients diagnosed with SGC (cases 1...
Citations
... Preventive role of CDK1, CDKN2A and CCNE1 is also found in patients with SGC through the overexpression of these genes. 19,20 Although, the role of CDKN2A in targeting CDK1 and CCNE1 is reported to be insu cient for the prevention of SGC, the mutation and functional inactivation of CDKN2A are vital for understanding its interplay in the cell cycle regulation pathway. 21 Immune checkpoint regulator ...
Objectives
This review aimed to conduct a comprehensive analysis of mismatch gene defect, cell cycle dysregulation, and anomalous signaling—including Wnt/β-catenin, hedgehog, and caspase-3/YAP signaling—in relation to the phenotypic presentation of eyelid sebaceous gland carcinoma (SGC) patients. This review also includes in-silico analysis to explore selectively expressed proteins (SEPs) through network-based analysis.
Methods
A thoroughly literature search was performed using PubMed, Google scholar, and Web of Science databases to provide updated knowledge on critical genes and related signaling pathways in SGC pathogenesis by using specific and relevant terms. A protein-protein interaction (PPI) network was constructed for selected genes with strong evidence from the literature, using STRING 11.0 database and Cytoscape 3.7.1 software.
Results
This review highlights crucial genes and proteins involved in the progression of eyelid SGC. Mismatch repair (MMR) genes are integral to SGC in patients, essential for maintaining genomic integrity. This review also describes mutational analysis, noting that mutations primarily occur in MLH1 and MSH2, followed by MSH6, PMS2 and p53. In patients with SGC, mutations or dysregulation of factors or genes involved in hedgehog, β-catenin, caspase-3/YAP, and C-MYC-AR-p53 signaling are crucial during tumorigenesis. The network-based approach elucidates the roles of essential genes, including MMR genes, and experimentally determines interactions, co-expression, and combined scores. The lowest combined scores were observed for CTNNB1 and SHH. Additionally, the role of immune checkpoint regulators—including PD-1, PD-L1, and CTLA—is investigated, revealing that their dysregulation leads to poor cancer cell presentation to immune cells.
Conclusion
We summarize the literature on crucial genes (e.g., MMR genes) and related signaling pathways (e.g., Wnt/β-catenin, hedgehog, and Capspase-3/YAP signaling) in the pathogenesis of eyelid SGC. Eyelid SGC is an aggressive tumor typically associated with MMR gene defects compared to other critical genes involved in tumorigenesis. In-silico analysis provides a better understanding of critical genes expressed in sebaceous glands and their role in SGC pathogenesis. These differentially expressed genes in tumor cells could improve SGC diagnosis and serve as potential targets for drug therapy.
... CDKN2A is involved in cell-cycle progression and has been validated to play an important role in many kinds of cancers, including pancreatic cancer (Gu et al., 2020), sebaceous gland carcinoma of the eyelid (Yunoki et al., 2020) and so on. Our results further confirmed the role of CDKN2A in ccRCC. ...
Background: Cuprotosis is a new form of programmed cell death induced by copper. We explored the correlation of cuprotosis with clear cell renal cell carcinoma (ccRCC) and constructed a cuprotosis-related signature to predict the prognosis of patients with ccRCC.
Methods: The clinical and transcriptomic data of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA), cBioPortal, and GEO databases, and cuprotosis-related gene sets were contained in the previous study. A cuprotosis-related signature was developed based on data from TCGA and verified by data from cBioPortal and GEO databases. The immune cell infiltrates and the corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correlation of the signature risk score with immune therapy response.
Results: A signature containing six cuprotosis-related genes was identified and can accurately predict the prognosis of ccRCC patients. Patients with downregulated copper-induced programmed death had a worse overall survival (hazard ratio: 1.90, 95% CI: 1.39–2.59, p < 0.001). The higher signature risk score was significantly associated with male gender ( p = 0.026), higher tumor stage ( p < 0.001), and higher histological grade ( p < 0.001). Furthermore, the signature risk score was positively correlated with the infiltration of B cells, CD8 ⁺ T cells, NK cells, Tregs, and T cells, whereas it was negatively correlated with eosinophils, mast cells, and neutrophils. However, no correlation between cuprotosis and response to anti-PD-1 therapy was found.
Conclusion: We established a cuprotosis signature, which can predict the prognosis of patients with ccRCC. Cuprotosis was significantly correlated with immune cell infiltrates in ccRCC.
... Furthermore, our results revealed additional genes like cyclin-dependent kinase 1 (CDK1), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) that exhibited signi cantly higher expression in the OC tissues. A recent study by Yunoki and coworkers demonstrated that these three genes were signi cantly upregulated in the sebaceous gland carcinoma (SGC) of eyelid [14]. Interestingly, CDKN2A is the most widely studied gene for its tumor suppressive activity. ...
Background: Given the known lethality of highly frequent ovarian cancer (OC) among females, it is imperative to investigate potential biomarkers of prognostic and therapeutic significance. The objective of this study was to identify significant differentially expressed genes (DEGs) with poor prognosis and to explore their underlying mechanisms.
Methods: We acquired three microarray datasets (GSE14407, GSE36668 and GSE18520), available from the public database GEO. We compared a total of 72 cancerous and 26 normal samples originating from ovarian tissues. GEO2R and Venn diagram tools were used to obtain DEGs, followed by the gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analysis via Database for Annotation, Visualization and Integrated Discovery (DAVID). Subsequently, protein-protein interaction (PPI) network was constructed and visualized in Cytoscape.
Results: Among three analyzed datasets, a total of 232 DEGs were common. The upregulated 108 genes were significantly enriched in the cell adhesion, cellular response to interleukin-1, positive regulation of transcription from DNA/RNA, and transcription, extracellular matrix/region, anchored membrane component, cell junction and golgi membrane, sequence-specific DNA binding, transcription factor activity, RNA polymerase II regulatory region, and DNA binding. The PPI network analysis via MCODE plug-in revealed a total of 14 upregulated genes. Kaplan-Meier plotter analysis revealed that 9 genes were associated with significantly worse survival among OC patients while 4 genes exhibited no significant effect. Gene Expression Profiling Interactive Analysis (GEPIA) showed that 13 DEGs had significantly higher expression in the ovarian cancerous tissues compared to the normal ones. Repeated KEGG analysis showed that 11 genes (CDC6, CCNE1, BUB1B, CCNB2, BUB1, SFN, TTK, CDC20, PTTG1, CDK1 and CDKN2A)) were mainly associated with cell cycle while 2 genes (SFN and RRM2) were related to p53 signaling pathway.
Conclusion: Our findings identify potential upregulated DEGs of prognostic value among OC patients. This will facilitate to understand the underlying OC mechanisms and to implement targeted therapeutic measures.
... High expression of growth factor receptors such as vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and platelet-derived growth factor receptor are also known as clinicopathologic features of SGc (18). Moreover, expression levels of prognosis factors such as zinc finger E-box binding homeobox 2 (ZeB2) (19), human epidermal growth Bioinformatics analysis of the microRNA-mRNA network in sebaceous gland carcinoma of the eyelid factor receptor 2 (20) and aldehyde dehydrogenase 1 (21) were known to be used for the prognosis prediction. in our previous study, we revealed the mRNA expression profiles of SGc and identified the gene network consisting of cell cycle related genes including cyclin dependent kinase inhibitor 2a (CDKN2A), cyclin dependent kinase 1 (CDK1) and cyclin e1 (CCNE1) (22). To date, although a number of studies have been conducted to explore novel therapeutic targets, no specific protein expression patterns have been identified for either primary or metastatic lesions of SGc (18). ...
... in the present study, a small rna-sequencing analysis were performed to reveal the mirna expression profiles of SGc and to identify differentially expressed mirnas common to the tumor samples from three patients with SGc compared to a sebaceous adenoma control sample. in addition, we conducted integrated bioinformatics analyses to identify biological functions, canonical pathways and mirna-mrna networks of SGC using the data of mRNA expression profiles obtained from the same tumor sample sets in our previous study (22). ...
... In our previous study, mRNA expression profile data of the same sample set were obtained using the Genechip system with clariom S human arrays (affymetrix) (22). Briefly, the raw intensity data (Gene Expression Omnibus; accession no. ...
Sebaceous gland carcinoma (SGC) of the eyelid is an uncommon aggressive tumor with a relatively high rate of local recurrence and a poor prognosis following metastasis. However, the molecular mechanisms underlying the pathogenesis of SGC remain unclear. The purpose of the present study was to clarify microRNA (miRNA) expression profiles in SGC and to explore novel miRNA‑mRNA networks of SGC. A small RNA‑sequencing analysis was performed to identify miRNAs differentially expressed between SGC and sebaceous adenoma control samples. Bioinformatics analyses were conducted to reveal biological functions, canonical pathways and molecular interaction networks using integrated miRNA‑mRNA datasets, including mRNA expression profiles of SGC from our previous study. The present results demonstrated that 16 upregulated miRNAs and 516 downregulated mRNAs were associated with loss of lipid metabolism function and enriched in cholesterol biosynthesis pathways. By contrast, 29 downregulated miRNAs and 194 upregulated mRNAs were mainly associated with the promotion of cell survival and proliferation in addition to enrichment of DNA damage‑induced cell cycle‑regulation pathways. Furthermore, network analyses revealed that the upregulated miRNAs, miR‑130a‑3p and miR‑939‑5p, and the downregulated miRNAs, miR‑146a‑5p, miR‑149‑3p, miR‑193a‑3p, miR‑195‑5p and miR‑4671‑3p, could be upstream regulators related to these functional changes of SGC. These results improved the understanding of molecular mechanisms of SGC and may help to improve the diagnosis of SGC.
The Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels.
Albumin is successfully applied as a nanocarrier in the clinical nanomedicine and the abnormal miR-503 expression is related to the development of myocardial infarction (MI). This study aimed to explore the efficacy of albumin nanoparticles (NPs)-based delivery of miR-503 antagonist for MI therapy. After establishment of an animal model of MI, mice were administered albumin NPs loaded with miR-503 agonist or antagonist, normal saline (model group), CCNE1 agonist, or CCNE1 inhibitor ( n = 10) with 10 mice sham-operated. Murine peripheral blood was collected to measure endothelial progenitor cells (EPCs) in peripheral blood along with analysis of miR-503, CCNE1 and SDF-1 α expression by RT-qPCR, formation of new blood vessels and EPCs viability. Albumin NPs loaded with miR-503 antagonist increased EPCs number and new blood vessels formation, accompanied with down-regulation of miR-503 and up-regulation of SDF-1 α and CCNE1. The NPs carrying miR-503 agonist exerted an opposite activity with less EPCs and new blood vessels than sham-operated group without significant difference between agonist group and model group. Besides, miR-503 antagonist promoted EPCs viability. Furthermore, inhibition of CCNE1 suppressed blood vessel formation and miR-503 targeted CCNE1. In conclusion, albumin-based NPs loaded with miR-503 antagonist decrease miR-503 expression and increase CCNE1 and SDF-1 α expression to promotes EPCs viability and enhance the formation of new blood vessels, thereby improving MI.
Meibomian gland carcinoma (MGC) is a malignant eyelid tumor with a high malignancy degree and poor prognosis. However, the lack of suitable cell and animal models has limited the study of MGC pathogenesis. In the present study, we established and identified one human MGC cell and one meibomian gland (MG) cell model by fresh surgical resection tissue block primary culture and differentially expressed gene assays. The outgrowth of MGC and MG cells was periodically observed after primary culture, and the first passage of MGC cells proceeded on the 14th day, whereas that for MG cells after three weeks. Cell ultrastructures were observed by transmission electron microscopy (TEM). Immunofluorescence staining showed that MGC and MG cells were both positive for cytokeratin (CK) and androgen receptor (AR). Orange granules were observed in the cytoplasm of MGC and MG cells using Oil red O staining, but they were stronger for MG cells than for MGC. CCK-8 detection demonstrated that the proliferation ability of MGC cells was stronger than that of MG cells. Moreover, during RNA sequence analyses, 3023 differential expressed genes were detected between MGC and MG cells. These genes were involved in biological processes such as cell division and positive regulation of cell migration; the signaling pathways mainly covered cell cycle and DNA replication. Further, the tumorigenic potential of MGC cells was examined by inoculating them subcutaneously into the right abdomen of three severely immunodeficient NOD -SCID mice. Transplanted tumors formed on day 11 after inoculation. The xenograft mouse tissues retained the same histological characteristics as the human MGC original tumor and MGC primary cells. Altogether, these results showed that the MGC and MG models were successfully cultured and established, and differentially expressed genes were successfully detected. We provided a useful model and molecular basis for studying the biological characteristics and pathogenesis of human MGC.
