The Expression And Significance Of HDAC1 And E2F1 In Clear Cell Renal Cell Carcinoma

Objective: The morbidity and mortality of renal cell carcinoma(RCC), a common genitourinary system malignancy, of which 60% to 85% is clear cell renal cell carcinoma(cc RCC), is on rise in recent years. The patients usually have no obvious clinical symptoms, and less than 1/3 patients with the typical symptoms of hematuria, waist discomfort and waist mass; And the main method in diagnosis of this disease is imaging examination, such as ultrasonic, CT and MRI. Early Clear cell renal cell cancer is not easy to be found, even if the improvement of the present national health consciousness and medical technology. The incidence rate and the detection rate of cc RCC are significantly increased. And the cases with no clinical manifestations or occasionally found in the physical examination are increasing. But a part of patient are still diagnosed lately; maybe some patients had distant transfer. Therefore, it is important for the early diagnosis and treatment to explore the mechanism of occurrence and development of cc RCC.Transcription factor E2F1(E2F1), an important member of the E2 Fs transcription factor family, plays a critical role in early cell cycle progression and apoptosis. Histone deacetylase 1(HADC1) is a member of the Zinc-dependent family of histone deacetylases, which binds to E2F1 and downregulates acetylation level of E2F1 through Rb/E2 F pathway. E2F1 dysfunction can lead to the proliferation of malignant cells to induce tumorigenesis. A large number of studies have indicated that HDAC1 plays a critical role in the epigenetic studies of tumors, which is related to the transcription expression of E2F1, the early cell cycle progression and apoptosis. There have been ongoing researches about the role of epigenetics. Therefore, the aim of this study is to clarify the expression of protein and m RNA of HDAC1 and E2F1 in cc RCC tissues, the peritumoral tissues and the normal renal tissues by immunohistochemical method and RT-PCR method, and to discuss the role they play in the occurrence and development in cc RCC.Methods: From July 2013 to July 2014, we collected 51 cases of cc RCC tissues(pathologically confirmed)in the department of Urology Surgery, the second Hospital of Hebei Medical University. We selected 24 cases of the peritumoral tissues( away from the cancerous tissues in 5cm, confirmed by pathology as normal renal tissues) in 51 cases of cc RCC simples. According to the Fuhrman three-level classification standard recommended by WHO in 1997, we defined histologic classification;According to TNM staging criteria of kidney cancer recommended by AJCC in 2010, we defined the clinical stage. All the cases were not carried out preoperative radiotherapy, chemotherapy and immunotherapy. The specimens were divided into 2 groups, one group was fixed by 10% formaldehyde solution, then paraffin blocks embedded and sliced; another group was immediately frozen in liquid nitrogen after the operation and stored at-80 refrigerator. Immunohistochemistry ℃ and RT-PCR were used to analyze the protein and m RNA expression of HDAC1 and E2F1 in cc RCC tissues and the control group tissues. And further estimated their relationship with clinical dates by statistical software. We analyzed the different immunohistochemical staining positive expression rate of HDAC1 and E2F1 among the groups by c2 test or Fisher’s exact probability test by SPSS19.0 statistical software; P<0.05 was considered statistically significant. We applied t test to analyze the results( sx ±) of the absorbance ratio among the groups. P<0.05 was considered statistically significant.Results:1 Immunohistochemical staining results indicated that the positive expression rates of the protein of HDAC1 was higher in cc RCC tissues(62.7%) than that in the control group tissues(25%)(P<0.05). The positive expression rates of the protein of E2F1 was higher in cc RCC tissues(70.6%) than that in the control group tissues(37.5%)(P<0.05). The expression of the protein of HDAC1 and E2F1 was not associated with sex, age and tumor sizes(P>0.05), but with the histological grade and clinical stage(P<0.05).2 RT-PCR results demonstrated that the relative expression quantity of the m RNA of HDAC1 was higher in cc RCC tissues(0.351±0.151) than that in the control group tissues(0.102±0.044)(P=0.000).The relative expression quantity of the m RNA of E2F1 was higher in cc RCC tissues(0.318±0.092) than that in the control group tissues(0.135±0.032)(P=0.004).Conclusions:1 The high expression of HDAC1 and E2F1 in cc RCC was higher than that in the peritumoral tissues, and associated with the histological grade and clinical stage; The up-regulated expression was related to the increase in the tissue malignant degree, which may be associated with the progress of cc RCC.2 It may be an effective way to collectively detect the expression of HDAC1 and E2F1 for predicting the biological behavior of cc RCC, the early diagnosis and treatment; and HDAC1 and E2F1 may be a potential therapeutic target for cc RCC.