Enhanced Expression Of DNMT1and HDAC1Correlates With Differentiation Degree Of Renal Clear Cell Carcinoma

Renal clear cell carcinoma (RCCC) accounts for78.6%in renal cellcarcinoma (RCC) and33-50percent of RCCC is asymptomatic. Due to lackof effective treatment to advanced RCCC, about40%patients will suffer fromrecurrence and metastasis even after surgical therapy and their averagesurvival time is less than1year. With early diagnosis and treatment, the5-yearsurvival rate of RCCC patients could be up to94%. Therefore,we need tofurther investigate the molecular mechanisms in the formation and progressionof RCCC, in order to find new diagnotic and therapeutic methods of earlyRCCC. The role of DNA methyltransferase1(DNMT1) and histoneacetyltransferase1(HDAC1) has been deeply known in the developmentalprocess of RCCC. It shows that they maybe played an important role in theprogression of RCCC. The expression of DNMT1and HDAC1is significantlyincreased in many tumor tissues, causing genome instability, activation ofproto-oncogenes and inactivation of anti-oncogenes. Therefore, in-depth studyof changes of DNMT1and HDAC1, the development process of RCCC mayreveal the molecular biological mechanism of RCCC invasion and providereference indexes for clinical diagnosis, treatment and prognosis.Objective:This study is designed to investigate the expression of DNMT1andHDAC1in RCCC and the relationship with the clinical pathologiccharacteristics. Besides, this study also analyzes the correlation between theexpression level of DNMT1and HDAC1, in order to provide new clues forclinical diagnosis and treatment of RCCC.Method:Immunohistochemistry was used to investigate the protein expression ofDNMT1and HDAC1in57cases of RCC(clear cell type),33cases of peritumoral tissues and15cases of normal renal tissues, and to analyze itsrelationship with the clinical pathologic characteristics (age, gender,tumorsize,grade of differentiation TNM staging and lymph node metastasis).SPSS13.0was used to analyze the data of the experiment. P≤0.05wasindicating significant difference.Results:1. The positive expression rate of DNMT1in RCCC, peritumoral tissuesand normal renal tissues were71.9%,21.2%and20.0%respectively; thepositive expression of DNMT1in RCCC compared with that in peritumoraland normal renal tissues was significantly different (P<0.05).The positive expression rate of HDAC1in RCCC, peritumoral tissuesand normal renal tissues were59.6%,36.3%and13.3%respectively; thepositive expression of HDAC1in RCCC compared with that in peritumoraland normal renal tissues was significantly different (P<0.05).2. The expressions of DNMT1and HDAC1protein were not relatedwith the age, gender, the tumor size, and lymph node metastasis (P>0.05),whereas they were strongly correlated with the degree of differentiation andTNM staging(P<005).3. Protein expression of DNMT1was positively correlated withHDAC1.Conclusions:1. The expression of DNMT1and HDAC1protein in RCCC tissueswas higher than normal renal tissues that was an early event and maybecorrelated with the occurrence and development of RCCC.2. The expression of DNMT1and HDAC1was significantly correlatedwith the degree of differentiation and clinical pathological staging.Up-regulated expression of them correlated with malignant degree of tissuerising. The enhanced level of DNMT1and HDAC1may prompt the progressof RCCC and reflect the malignant biological behavior of RCCC and serve asnew prognostic factors of RCCC.3. The expression level of DNMT1and HDAC1was positive correlated, and may both prompt the occurrence and development of RCCC.