| Background:Bladder cancer is one of the most common urologic oncology. According to Cancer Registration Center data of China,the incidence of bladder cancer was up to 7.49/100,000 during 2008 year in China, and men in urban had the highest incidence(13.07/100,000), but the international standardized incidence rate was 4.53/100,000. Data also showed that bladder cancer is the highest incidence of male genitourinary malignancies. Bladder urothelial carcinoma accounted for more than ninety percent of bladder cancer. The recurrence rate of transurethral resection of bladder tumor is very higher, 1-year recurrence rate is 15-61%, 5-year is up to 31-78%. As the bladder urothelial carcinoma has a higher recurrence rate, requiring long-term monitoring and treatment of patients is bound to bring greater economic pressure. Thus, for the best treatment period, Further progress of bladder urothelial carcinoma, and reducing the economic pressure of the patient, bladder urothelial carcinoma is more need for an effective method or technology to timely diagnosis and monitoring,Cystoscopy and urine cytology about the diagnosis of bladder urothelial carcinoma are classical methods. Cystoscopy has a high sensitivity and specificity, but it also has trauma and possible complications, such as urinary tract infection, pain, bleeding. Check also leads to higher costs during long-term. Urine cytology in the diagnosis of NMIBC has high specificity(86-90%), But the sensitivity of urine cytology is low, typically 33-48%, and for low-grade NMIBC, whose accuracy is less than 60%. Currently, the US Food and Drug Administration has approved the nuclear matrix protein 22(NMP22), bladder tumor antigen(BTA) and ImmunoCyt / uCyt + used in clinical diagnosis of bladder cancer. But the test results are easy to be influenced by other factors, leading to a high false positive rate. Currently, those could not replace cystoscopy and are recommended for clinical work. Therefore, new biomarkers for diagnosing and monitoring bladder urothelial carcinoma are very.important.MicroRNA(miRNA, miR) is a tiny non-coding RNA molecule, which usually consists of 18-24 nucleotides, and combines with the C-terminal untranslated region of messenger RNA, playing role in the process of protein expression as after transcription regulation. The literature showed that miRNA molecules are stable in tissue, blood and urine samples, and miRNA molecules of the blood and urine can be used as disease diagnosis and prognosis of non-invasive markers. Therefore, the experiment will use this point to explore miR-21, miR-155 molecule expression of the serum and urine in bladder urothelial carcinoma, looking for stronger specificity, higher sensitivity of biomarkers.Detecting protein content in serum and urine is the classic method of disease diagnosis, such as PSA diagnosing prostate cancer. Osteopontin(OPN) and TGFBI are two of the most common proteins, which are highly express in bladder urothelial carcinoma. Both may be abnormal expressed in serum andurine of bladder urothelial carcinoma by reading literature. In this study, enzyme-linked immunosorbent assay(ELISA) will be uses to research the content OPN and TGFBI in serum and urine of bladder urothelial carcinoma, to further analysis the relations with clinical pathology, and clinical value for the diagnosis of bladder urothelial carcinoma. Objective:Serum and urine samples and clinical data of patients with bladder urothelial carcinoma, benign disease and healthy volunteers were collected, respectively, in Lanzhou Military General Hospital. RT-PCR and double antibody sandwich(ELISA) were used to detect the expression of miR-21, miR-155, OPN and TGFBI in serum, urine samples of three groups.1. To understand whether miR-21, miR-155, OPN and TGFBI are expressed different in serum and urine specimens of three groups;2. To understand whether miR-21, miR-155, OPN, TGFBI are expressed different in serum and urine specimens of different stages and grades of bladder urothelial carcinoma;3. According test results of miR-21, miR-155, OPN and TGFBI in serum and urine, each or combine of them were investigated to diagnose sensitivity and specificity of bladder urothelial carcinoma. Methods:1. RT-PCR method was used to detect the expression of miR-21 and miR-155 in serum and urine samples of three groups;2. ELISA method was used to detect the expression of OPN and TGFBI in serum and urine samples of three groups;3. According to receiver operating characteristiccurves(ROC) and area under the curve(AUC) of miR-21, miR-155, OPN, TGFBI in serum and urine, four biomarkers was evaluated for the diagnostic value of bladder urothelial cancer. Results:1. The serum and urine miR-21 relative expression levels were significantly higher in the cancer patients than in the benign disease group and healthy group(P<0.01), respectively. The serum miR-21 relative expression levels of patients with urothelial carcinoma were associated with TNM stage(P<0.01), pathologic grade(P<0.01) and metastasis(P<0.01), but the urine miR-21 relative expression levels were only associated with pathologic grade(P<0.01) and metastasis(P<0.05). The sensitivity of serum and urine miR-21 to diagnose bladder urothelial carcinoma were 90.0%, 82.5%, and specificity of 80.0%, 76.7% respectively.2. The serum miR-155 relative expression levels were significantly higher in the cancer patients than in the benign disease group and healthy group(P<0.01), respectively.But urine miR-155 relative expression levels were only significantly higher in the cancer patients than in the healthy group(P<0.05). The serum miR-155 relative expression levels of patients with urothelial carcinoma were associated with TNM stage(P<0.05) and metastasis(P<0.05), but the urine miR-155 relative expression levels were only associated with metastasis(P<0.05). The sensitivity of serum and urine miR-155 to diagnose bladder urothelial carcinoma were 82.5%, 62.5%, and specificity of 63.3%, 73.3%, respectively.3. The serum and urine OPN expression levels were significantly higher in the cancer patients than in the benign disease group and healthy group(P<0.05), respectively. The serum OPN expression levels of patients with urothelial carcinoma were associated with TNM stage(P<0.05), pathologic grade(P<0.05) and metastasis(P<0.05), but the urine OPN expression levels were not associated with the clinical pathological features(P>0.05). The sensitivity of serum and urine OPN to diagnose bladder urothelial carcinoma were 90.0%, 77.5%, and specificity of 80.0%, 80.0%, respectively.4. The serum and urine TGFBI expression levels were significantly higher in the cancer patients than in the benign disease group and healthy group(P<0.05), respectively. The serum and urine TGFBI expression levels of patients with urothelial carcinoma were not associated with the clinical pathological features(P>0.05). The sensitivity of serum and urine TGFBI to diagnose bladder urothelial carcinoma were 65.0%, 67.5%, and specificity of70.0%, 76.7%, respectively. Conclusion:The expression levels of miR-21, miR-155, OPN, TGFBI in serum and urine bladder urothelial carcinoma are abnormally high, the miR-21, OPN expression level of which are higher,and the expression level of serum is higher than from urine. They may have certain relationship with the occurrence, development and prognosis of the tumor, closely related to the clinical and pathological characteristics of patients. They may become new biomarkers about early diagnosis and prognosis of bladder urothelial carcinoma in the future, even for ureteral carcinoma, carcinoma of the renal pelvis, symptoms of blood in the urine of transitional epithelial carcinoma patients to provide a method of early diagnosisand, and may also provide the new and potential therapeutic targets for bladder urothelial carcinoma. |
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