scholarly journals Promoter Region Hypermethylation and mRNA Expression ofMGMTandp16Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Vikram Bhatia ◽  
Madhu Mati Goel ◽  
Annu Makker ◽  
Shikha Tewari ◽  
Alka Yadu ◽  
...  

Promoter methylation and relative gene expression of O6-methyguanine-DNA-methyltransferase (MGMT) andp16genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation ofMGMTandp16genes was observed in 59% (P=0.0010) and 57% (P=0.0016) of tissue samples, respectively, and 39% (P=0.0135) and 33% (P=0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P=0.0001) and 82% (P=0.0001) in tissue and 57% (P=0.0002) and 70% (P=0.0001) in blood, respectively. Significant downregulation ofMGMTandp16mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing ofMGMTandp16genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC.

Author(s):  
Sedigheh KHEIRANDISH ◽  
Nosratollah ESHGHYAR ◽  
Farzad YAZDANI ◽  
Pouyan AMINI SHAKIB ◽  
Ali HOSSEINI-BERESHNEH ◽  
...  

Background: Oral squamous cell carcinoma (OSCC) is one of the most important types of oral malignancies. DKK gene family members as well as DKK2/4 have critical roles in regulation of Wnt signaling as one of the main determining pathway in oral carcinogenesis. This study aimed to identify promoter methylation status of DKK2/4 genes to provide possible biomarkers for early detection and treatment of OSCC patients. Methods: A case control study was performed on 31 fresh tissues obtained from oral cavity of patients affected by OSCC and 31 fresh corresponding tissues from normal healthy controls in Tehran and, between the years of 2016-2018. Purified DNA from tissue samples was subjected to bisulfite treatment and then methylation specific polymerase chain reaction (MSP-PCR) was carried out on treated DNA samples. Results: DKK4 promoter was methylated in none of OSCC samples while it was methylated in 16.1% of healthy controls. 16.1% of OSCC samples were detected to be semimethylated and 22.6% of healthy normal samples were methylated for DKK2 promoter gene. Meaningful difference was found in DKK4 promoter methylation among OSCC patients and healthy controls. Significant correlation was found between DKK4 promoter methylation and tumor grade. The age of all enrolled samples was demonstrated to have strong effect on promoter methylation of studied genes. Conclusion: Hypomethylation of DKK2 and DKK4 genes in higher grades of OSCC samples may indicate the pivotal role of their expression in tumor cells invasion and progression through modulation of Wnt signaling pathway. Further study required to determine simultaneous expression of those genes and Wnt signaling elements at mRNA and protein levels.


Author(s):  
Krishnapriya Umashankar ◽  
J. Selvaraj ◽  
Pratibha Ramani

Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignancies which accounts for 90% of oral cancer worldwide. The 5 year survival rate of OSCC is not more than 60% due to tumor metastasis and subsequent recurrence. Aim: To compare the gene expression of ITG β-1, MMP9 and Vimentin in OSCC tissue samples and normal tissue samples and to correlate the expression levels of these molecules with the pathological grading and survival in OSCC patients. This would facilitate the understanding of EMT in OSCC progression thereby targeting this pathway for treatment of OSCC patients in near future. Materials and Methods: 10 OSCC samples as well as normal healthy samples were collected and RNA isolation was done using TRIR kit, and then subjected to cDNA synthesis using ITG β-1, MMP9 and Vimentin primers. Real time PCR was performed using gene specific primers at 40 cycles. The results were retrieved, tabulated and analyzed. Results: The current research results revealed that there were up regulation of mRNA expression in ITG β-1, MMP9 and Vimentin in OSCC patients than in healthy individuals. On comparison, MMP9 showed highest mRNA expression levels than ITG β-1 and Vimentin Conclusion: Over expression of ITG B-1, MMP9, Vimentin plays a crucial role in progression of oral cancer and targeting EMT molecules could be an effective targeted approach for OSCC.


2020 ◽  
Vol 99 (6) ◽  
pp. 666-675 ◽  
Author(s):  
L. Wen ◽  
W. Mu ◽  
H. Lu ◽  
X. Wang ◽  
J. Fang ◽  
...  

Increasing evidence has revealed a significant association between microorganisms and oral squamous cell carcinoma (OSCC). Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, is considered an important potential etiologic agent of OSCC, but the underlying immune mechanisms through which P. gingivalis mediates tumor progression of the oral cancer remain poorly understood. Our cohort study showed that the localization of P. gingivalis in tumor tissues was related to poor survival of patients with OSCC. Moreover, P. gingivalis infection increased oral lesion multiplicity and size and promoted tumor progression in a 4-nitroquinoline-1 oxide (4NQO)–induced carcinogenesis mouse model by invading the oral lesions. In addition, CD11b+ myeloid cells and myeloid-derived suppressor cells (MDSCs) showed increased infiltration of oral lesions. Furthermore, in vitro observations showed that MDSCs accumulated when human-derived dysplastic oral keratinocytes (DOKs) were exposed to P. gingivalis, and CXCL2, CCL2, interleukin (IL)–6, and IL-8 may be potential candidate genes that facilitate the recruitment of MDSCs. Taken together, our findings suggest that P. gingivalis promotes tumor progression by generating a cancer-promoting microenvironment, indicating a close relationship among P. gingivalis, tumor progression of the oral cancer, and immune responses.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yuyang Li ◽  
Jia Li ◽  
Jingchun Sun ◽  
Yingkun Liu ◽  
Dingkun Liu ◽  
...  

Purpose. To examine the expression of RAD51 in oral squamous cell carcinoma (OSCC) and analyze its connection with pathological grade, clinical stage, and lymphatic metastasis potential. Methods. For this study, 74 OSCC samples, 15 normal mucosa tissues, and 11 normal skin tissue samples were collected. RAD51 expression was investigated using immunohistochemistry. A follow-up visit was used to assess the prognosis of each patient. We compared RAD51 expression in oral mucosa epithelial cells (OMECs), keratinocytes, and tongue squamous cell carcinoma cells (TSCCs) by Western blot analysis. Results. RAD51 expression was higher in tumor cells than in normal mucosal tissues. In addition, RAD51 expression was associated with higher tumor differentiation (P<0.05). Also, RAD51 expression was higher (P<0.05) in patients with lymphatic metastases, and relapse rates were also higher in patients with elevated RAD51 levels (P=0.052). In addition, RAD51 expression levels were highest in the skin keratinocytes, followed by the TSCCs and OMECs. Conclusion. A strong positive correlation was found between RAD51 expression and the degree of malignancy in OSCC patients, suggesting that RAD51 could be an excellent prognostic indicator for OSCC patients.


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