scholarly journals An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2092
Author(s):  
Luca Morandi ◽  
Silvia Sabattini ◽  
Andrea Renzi ◽  
Antonella Rigillo ◽  
Giuliano Bettini ◽  
...  

Background: Ultra-conserved non-coding elements (UCNEs) are genomic sequences that exhibit > 95% sequence identity between humans, mammals, birds, reptiles, and fish. Recent findings reported their functional role in cancer. The aim of this study was to evaluate the DNA methylation modifications of UNCEs in squamous cell carcinoma (SCC) from different mammal species. Methods: Fifty SCCs from 26 humans, 17 cats, 3 dogs, 1 horse, 1 bovine, 1 badger, and 1 porcupine were investigated. Fourteen feline stomatitis and normal samples from 36 healthy human donors, 7 cats, 5 dogs, 5 horses, 2 bovines and 1 badger were collected as normal controls. Bisulfite next generation sequencing evaluated the DNA methylation level from seven UCNEs (uc.160, uc.283, uc.416, uc.339, uc.270, uc.299, and uc.328). Results: 57/59 CpGs were significantly different according to the Kruskal–Wallis test (p < 0.05) comparing normal samples with SCC. A common DNA hypermethylation pattern was observed in SCCs from all the species evaluated in this study, with an increasing trend of hypermethylation starting from normal mucosa, through stomatitis to SCC. Conclusions: Our findings indicate that UCNEs are hypermethylated in human SCC, and this behavior is also conserved among different species of mammals.

Epigenomics ◽  
2020 ◽  
Author(s):  
Christopher Bockhorst ◽  
Jörn Dietrich ◽  
Timo J Vogt ◽  
Roland H Stauber ◽  
Sebastian Strieth ◽  
...  

1999 ◽  
Vol 23 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Jozsef Piffko ◽  
Agnes Bankfalvi ◽  
Ulrich Joos ◽  
Dietmar Ofner ◽  
Melanie Krassort ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3580
Author(s):  
Shatavisha Dasgupta ◽  
Patricia C. Ewing-Graham ◽  
Sigrid M. A. Swagemakers ◽  
Thierry P. P. van den Bosch ◽  
Peggy N. Atmodimedjo ◽  
...  

DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2915
Author(s):  
Bruna Pereira Sorroche ◽  
Fazlur Rahman Talukdar ◽  
Sheila Coelho Soares Lima ◽  
Matias Eliseo Melendez ◽  
Ana Carolina de Carvalho ◽  
...  

The identification of molecular markers in negative surgical margins of oral squamous cell carcinoma (OSCC) might help in identifying residual molecular aberrations, and potentially improve the prediction of prognosis. We performed an Infinium MethylationEPIC BeadChip array on 32 negative surgical margins stratified based on the status of tumor recurrence in order to identify recurrence-specific aberrant DNA methylation (DNAme) markers. We identified 2512 recurrence-associated Differentially Methylated Positions (DMPs) and 392 Differentially Methylated Regions (DMRs) which were enriched in cell signaling and cancer-related pathways. A set of 14-CpG markers was able to discriminate recurrent and non-recurrent cases with high specificity and sensitivity rates (AUC 0.98, p = 3 × 10−6; CI: 0.95–1). A risk score based on the 14-CpG marker panel was applied, with cases classified within higher risk scores exhibiting poorer survival. The results were replicated using tumor-adjacent normal HNSCC samples from The Cancer Genome Atlas (TCGA). We identified residual DNAme aberrations in the negative surgical margins of OSCC patients, which could be informative for patient management by improving therapeutic intervention. This study proposes a novel DNAme-based 14-CpG marker panel as a promising predictor for tumor recurrence, which might contribute to improved decision-making for the personalized treatment of OSCC cases.


2021 ◽  
Vol 11 (2) ◽  
pp. 308-314
Author(s):  
Zengbo Wu ◽  
Yan Yan ◽  
Xianzhuo Chen ◽  
Yanling Liu ◽  
Dinggen Chen

miR15b and SALL4 are involved in a variety of tumor progression. The roles of miR15b and SALL4 in oral squamous cell carcinoma (OSCC) remains unclear. The tumors and normal mucosa of OSCC patients were collected to detect miR15b and SALL4 level by Real-time PCR and analyze their correlation with OSCC clinicopathological features. Oral cancer Tca8113 cells were separated into control group; miR15b mimics group and miR15b inhibitor group followed by analysis of SALL4 expression, cell survival by MTT assay; cell invasion by Transwell chamber assay, as well as expression of N-cadherin and Vimentin and correlated with TNM stage, tumor volume and metastasis, and positively with differentiation TGF-β by Western blot. miR15b expression was decreased and SALL4 expression was increased in OSCC tumor tissues. miR15b was negatively degree (P < 0.05), whereas, opposite correlation of SALL4 with the above parameters was found (P < 0.05). miR15b and SALL4 were negatively correlated. MiR15b mimics significantly up-regulated MiR15b, decreased SALL4 expression, inhibited Tca8113 cell proliferation and invasion, as well as reduced N-cadherin, Vimentin and TGF-βexpression (P < 0.05). Opposite results were found in MiR15b inhibitor group. MiR15b expression is decreased and SALL 4 is increased in OSCC tumor tissues. MiR15b and SALL4 is closely related to OSCC clinicopathological features. MiR15b regulates the expression of EMT-related genes and TGF-β, thereby altering the proliferation and invasion of OSCC cells.


2021 ◽  
Author(s):  
Jun Yang ◽  
Xiaohui Chen ◽  
Mingqiang Lin ◽  
Mengyan Zhang ◽  
Zhiping Wang ◽  
...  

Abstract Background: Lung cancer has become the leading cause of cancer-related deaths worldwide with a rising trend of incidence and mortality. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) account for the major numbers, which should be paid enough attention. Advanced glycation end products receptor (AGER) is a multi-ligand receptor that interacts with a wide range of ligands. Previous studies have shown that abnormal AGER expression is closely related to immune infiltration and tumorigenesis. Nevertheless, the AGER DNA methylation relationship between prognosis and infiltrating immune cells in LUAD and LUSC is still unclear. Results: Compared with the normal lung tissues, the expression level of AGER was significantly reduced in LUAD and LUSC. Low expression of AGER was markedly correlated with histology, stage, lymph node metastasis and Tumor protein 53 (TP53) mutation and could be used as a potential indicator of poor prognosis of LUAD and LUSC. Further analysis showed that copy number variation (CNV), mutation and DNA methylation involved in the low level of AGER. Additionally, we found that AGER DNA hypermethylation meant a worse prognosis in LUAD and LUSC. In addition, we also found that hypermethylated AGER was significantly correlated with tumor infiltrating lymphocytes. Conclusion: AGER may be a candidate for the prognostic biomarker of LUAD and LUSC related with tumor immune microenvironment.


2011 ◽  
Vol 53 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Sylvia Hartmann ◽  
Marcin Szaumkessel ◽  
Itziar Salaverria ◽  
Ronald Simon ◽  
Guido Sauter ◽  
...  

2021 ◽  
Vol 16 (10) ◽  
pp. S920-S921
Author(s):  
X. Wang ◽  
X. Xia ◽  
Y. Meng ◽  
W. Wang ◽  
W. Pi ◽  
...  

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 134-134
Author(s):  
Masayoshi Terayama ◽  
Teruki Hagiwara ◽  
Kazuhiko Yamada ◽  
Daisuke Soma ◽  
Kyoko Nohara ◽  
...  

Abstract Background Alcohol drinking and smoking are substantial risk factors of esophageal squamous cell carcinoma (ESCC) and are supposed to induce genetic mutations and epigenetic disorders, including aberrant DNA methylation. Previously, we have conducted transcriptome and methylome analyses of a paired specimen of ESCC and adjacent non-cancerous tissues and found that both gene expression and promotor methylation of PRSS27 were perturbed in ESCC. PRSS27 was a trypsin-like serine protease (also known as marapsin) and expressed in normal esophagus; however, little is known about the significance of PRSS27 expression in ESCC. In this study, we evaluated the expression of PRSS27 in many ESCC cases in relation with clinical features and the prognosis. Methods ESCC tissue specimens were obtained from 80 patients who had undergone esophagectomy between April 2008 and December 2016 in our hospital and were subjected to immunostaining for PRSS27. ESCC cases were classified into PRSS27-negative and PRSS27-positive groups and difference of clinical features and the prognosis between the groups was analyzed. Results The mRNA expression of PRSS27 was significantly decreased in ESCC compared with those in matched normal mucosa (P < 0.0001). Histologically, PRSS27 was highly expressed in spinous cells of suprabasal cell layer but not in basal cell layer of normal esophageal mucosa. In contrast, 37 of 80 (47%) ESCC exhibited decreased intensity of PRSS27 staining when compared with that in normal mucosa, and 53% (43/80) of ESCC showed almost no staining of PRSS27. Although the prognosis of PRSS27-positive cases were worse in trend than that of PRSS27-negative cases, there was no significant difference (P = 0.0763) Conclusion PRSS27 gene and protein expression was both downregulated in ESCC; its functional significance in relation to malignancy is underinvestigation. Disclosure All authors have declared no conflicts of interest.


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