Expression And Significance Of HMGB1 And Its Receptor RAGE In Bladder Urothelial Carcinoma

Background:Bladder cancer is one of the most common malignant tumors in the Department of Urology in our country, and almost of it is bladder urothelial carcinoma. Prediction of invasive bladder cancer is important in clinical work, which can provide significant prognostic information and guide clinical treatment. Currently, there is lack of a safe and effective biomarker to discovery and diagnosis of bladder tumor early, and it is still difficult to identification and investigation of invasion of bladder cancer early rely on existing cystoscopy and imaging technology. Studies found that high-expression of HMGB1 (high mobility group protein box-1) and its receptor RAGE (reeptor for advanced glycation end-products) was elevated in many tumor, indicate HMGB1-RAGE signal pathway may be closely associated with tumor development, invasion and metastasis. However, the association between HMGB1-RAGE signaling pathway and the bladder cancer is not clear, which is worth further study.Purpose:1. To study the expression of HMGB1 and RAGE in invasive bladder cancer tissues and adjacent normal bladder tissues;2. Analysis of the correlation between the expression of HMGB1 and RAGE in invasive bladder cancer.3. To study the expression and differences of RAGE and HMGB1 in different clinical stages and pathological grades of invasive bladder cancer, and to study the relationship between the expression level and the stage and grade of invasive bladder cancer.Method:Collection of bladder radical after resection of the pathological diagnosis of invasive bladder urothelial carcinoma tissue and its adjacent normal bladder tissue. Real-time PCR (realtime fluorescent quantitative PCR) and immunohistochemistry techniques were used to detect HMGB 1 and RAGE mRNA and protein expression of bladder carcinoma tissues and adjacent normal bladder mucosa tissue, and the use of statistical analysis of HMGB 1 and RAGE expression correlation, and the association between them and bladder cancer clinical stage, pathological grade.Result:(1) Real-timePCR results:the expression of RAGE and HMGB1 in invasive bladder cancer tissues was significantly higher than that in adjacent normal bladder tissues. The relative expression quantity of HMGB 1 in the cancer tissues was 2.34+ 0.71 and adjacent normal bladder tissues was 1.02+0.34 (P< 0.05). In 47 cases of bladder cancer tissue samples, according to the clinical classification, T21.900.58, T3-42.51+0.68 (P< 0.05). In no lymph node metastasis group was 2.03+0.50 and lymph node metastasis group was2.93+0.68, P< 0.05. According to the pathological grade, the low-grade group was 1.99+0.53, the high-grade group was 2.85+0.62, P<0.05 (If P<0.05, the difference was statistically significant).The relative expression of RAGE in cancer tissue was 1.65+0.46, and was 1.06 +0.27 in normal bladder tissue, and P<0.05. T2 stage of 1.49+0.53, T3-4 stage of 1.71+0.66, P>0.05, two groups had no statistical significance; In no lymph node metastasis group was 1.33+0.38, lymph node metastasis group was 2.27+0.69, P<0.05. Low-grade group was 1.43+0.60, high-grade group was 1.97+0.62, P<0.05.Immunohistochemistry results:the positive expression rates of HMGB1 in invasive bladder cancer tissues and adjacent normal tissues were 80.9%(38/47) and 27.7%(47/13), respectively (2=26.790, P<0.001). The positive expression rate of RAGE in bladder cancer tissues and adjacent normal tissues was 66%(31/47) and 19.1%(47/9) (2=21.063, P<0.001). HMGB1 and RAGE proteins were positive expression in 61.7%(29/47) bladder cancer cases together, and in 6.4%(3/47) tumor adjacent tissues cases, (?2=29.612, P<0.001).The expression of HMGB1 protein and RAGE protein was significantly positive correlation in bladder cancer tissue (P=0.002<0.01), the correlation coefficient was r=0.449. The positive expression of HMGB1, in high-grade group was 94.7%(18/19), in low-grade group was 71.4% (20/28),P=0.064>0.05; The positive expression of RAGE in the high-grade group accounted for 89.5%(17/19), low-grade group was 50%(14/28), P=0.006<0.05.Conclusion:HMGB1 and its receptor RAGE may play a role of oncogene in bladder urothelial carcinoma, the HMGB1-RAGE pathway is closely related with the invasion, lymph node metastasis and invasion of bladder urothelial carcinoma.