| Research background:Tongue squamous cell carcinoma(SCC)is a common malignancy in oral cancer,the main treatment methods are mainly operation at present,due to postoperative recurrence rate,high transfer rate and low overall survival rate in the five years after operation,the quality of life of patients was seriously affected.Therefore,to further study the pathogenesis of tongue squamous cell carcinoma,it is imperative to explore effective treatment strategies.With the continuous research of oncology,more and more pathogenesis has been revealed,Epigenetics is a hotspot in recent years,and more and more evidence shows that epigenetic modification plays an important role in the development and development of cancer.Epigenetics(Epigenetics)refers to changes that do not involve the sequence of genomic DNA,and the expression of genes is a stable,inheritable epigenetic change.In a broad sense,DNA methylation,histone modification,ubiquitination,genomic imprinting,RNA interference,chromatin remodeling,etc.are all categories of epigenetics,Content above all a change could lead to the occurrence of diseases,but unlike DNA sequence change,most of the epigenetic changes are reversible,which makes the cure of epigenetics change has infinite possibilities.Histone modification,as one of the most important kind of epigenetics,in eukaryotic cells plays an important role in regulating gene expression by Histone acetylation enzyme(HATs)and Histone acetylation enzyme(HDACs)protein family common regulation of the two groups of opposite.Histone deacetylase 2(HDAC2)is one of the most studied in HDACs.It has been proved that it plays an extremely important role in the occurrence and development of multiple cancers,and inhibiting the activity or expression of HDAC2 has become a very effective molecular target in the treatment of malignant tumors.EP300 is a member of the KATs family in HATs,Mutations in the EP300 can lead to a decline or rise in the level of acetylation of the entire genome,resulting in a genetic transcription imbalance that leads to the formation of cancer.Protein ubiquitination is a process of highly selective modification of targeted proteins under the regulation of various enzymes.Ubiquitination is the process by which ubiquitin proteins are degraded to free ubiquitin molecules under the action of ubiquitinase.In eukaryotic cells,ubiquitination and ubiquitination are the processes that maintain the normal physiological processes of cells by explaining the protein balance,and once the balance is broken,the disease can occur.CYLD(cylindromatosis,CYLD)is a common to ubiquitin enzyme,as a tumor suppressor in the body,In recent years,more and more studies have shown that it is important to regulate the balance of protein in cells by the way of ubiquitin signaling molecules.CYLD is closely related to the development and development of various human malignant tumors,which are most common in skin tumors.The regulation of transcription level of gene expression is critical in the physiological activities of cells.TATA binding protein is a transcription factor widely found in eukaryotic cells.Its main function is to form a transcription initiation complex with RNA polymerase Ⅱ.TBP is the only transcription factor that is the only one of the TATA binding proteins that can recognize the TATA box.RNA polymerase I,II,and III transcripts are required and have been shown to be closely related to the occurrence of multiple diseases.This study covers several aspects of epigenetics,mainly including histone modification,ubiquitination and DNA methylation.In this study,the gene expressions of mouse tongue squamous cell carcinoma was investigated,The expression abnormalities of HDAC2,CYLD,EP300 and TBP were detected in C57BL/6 mouse tongue carcinoma model by 4-nitroquinoline monoxide(4NQO).Is there any difference in the expression of the above gene in normal tongue mucosa,precancerous lesion and tongue carcinoma?What is the correlation between this difference and clinical pathological parameters such as tumor differentiation,lymph node metastasis,and patient survival rate?It is important to clarify the above questions to understand the role of HDAC2,CYLD,EP300 and TBP genes in the occurrence,treatment and prognosis of tongue cancer.Based on the above,this study intends to adopt the experimental method of immunohistochemistry.The expression of HDAC2,CYLD,EP300 and TBP in tongue mucosa,atypical hyperplasia and tongue squamous cell carcinoma were studied respectively.To analyze the correlation between the clinicopathological features of patients with tongue squamous carcinoma and the relationship between their expression and postoperative survival of tongue squamous carcinoma patients.To explore the theoretical basis and experimental basis for the prevention and treatment strategy of tongue squamous cell carcinoma.Objective:The expression of HDAC2,CYLD,EP300 and TBP in human tongue mucosa,atypical hyperplasia and tongue squamous cell carcinoma were studied.The correlation between its clinical pathological features and survival status was analyzed.Experimental evidence was provided to clarify the role of HDAC2,CYLD,EP300 and TBP in the occurrence,treatment and prognosis of tongue cancer.Methods:Specimens can be divided into:tongue squamous cell carcinoma group(n1=96、n2=45、n3=82、n4=92),tongue mucosa dysplasia group(ni=24、n2=13、n3=18、n4=26)and normal tongue mucosa group(ni=13、n2=10、n3=12、n4=12)immunohistochemical staining,Positive cells accounted for more than 5%of positive cells,and analyzed the correlation between their age,gender,TNM stage,lymph node metastasis and other clinicopathological factors.Kaplan-merier survival analysis was used to analyze the survival of patients.Results:1.The expression of HDAC2:HDAC2 expression and the patients’ age,sex,alcohol,tobacco,hobby,pathologic stage,lymph node metastasis,factors such as the differences between the meaningless(all P>0.05),but with TNM staging of cancer between statistically significant(P<0.001).HDAC2 protein in tongue squamous cell carcinoma patients with positive expression rate was significantly higher than that of atypical hyperplasia and normal tongue mucosa group(P<0.00).The expression of HDAC2 was not correlated with the postoperative survival of patients(P=0.184),and patients with lymph node metastasis were significantly shorter than those without lymph node metastasis(P=0.000).2.Expression of CYLD:There was no difference between tongue mucosa,atypical hyperplasia and tongue squamous cell carcinoma,the expression was not correlated with age,gender,smoking and alcohol addiction,pathological grading,lymph node metastasis,etc.The postoperative survival time of patients with lymph node metastasis was significantly shorter than those without lymph node metastasis(P=0.012).3.Expression of EP300:the positive expression rate in patients with tongue squamous cell carcinoma was significantly higher than that in the atypical hyperplasia group and the tongue mucosa group(P<0.000).The expression was not correlated with age,gender,alcohol and alcohol,pathological grading,lymph node metastasis,etc.The postoperative survival time of patients with lymph node metastasis was significantly shorter than those with no lymph node metastasis(P=0.040).4.Expression of TBP:There was no difference between tongue mucosa,atypical hyperplasia and tongue squamous cell carcinoma,The expression was not correlated with age,gender,smoking and alcohol addiction,pathological grading,lymph node metastasis,etc.There was no statistically significant difference between the expression and lymph node metastasis and postoperative survival of patients(P>0.05).Conclusion(s):The positive expression rate of HDAC2 and EP300 in human tongue squamous cell carcinoma was significantly higher than that in the atypical hyperplasia group and tongue mucosa group.The TNM staging of patients with HDAC2 positive expression was higher in stage Ⅲ--stage Ⅳ,suggesting that HDAC2 could be a reliable molecular reference index for the prognosis of tongue squamous carcinoma.The postoperative survival time of lymph node metastases was significantly lower than that of non-lymph node metastases. |
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