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دراسة Toll like receptors(TLR2& ( 4 ومؤشرات حيوية مختارة في المرضى المصابين بسرطان المثانة == Study Of Toll Like Receptors (TLR - 2 And 4) And Selected Biomarkers In Bladder Cancer Patients
Author name:
هدى سعدون البياتي
Supervisor name:
ميسون علي سليم | ناهي يوسف ياسين | عصام سلمان العزاوي
General topic:
Medicine
Specific topic:
Microbiology
Degree:
Doctorate
University:
Mustansiriyah University
Language:
English
University location:
Baghdad
First pages:
19T1152 - p.pdf
Abstract:
Worldwide, cancers of the urinary bladder are complex and involve genetic abnormalities and may be due to different environmental chemical carcinogens, as well as chronic infection like Schistosomiasis, all these will allow normal transitional cells to become cancerous which are typically transitional cell carcinoma(TCC).This study was conducted at AL - Yarmouk and Baghdad Teaching Hospitals in Baghdad from June 2013 to April 2014, of which urine and bladder tissue were taken from 57 bladder cancer patients and 80 controls to assess Interleukin - 8 (IL - 8), Matrix MetalloPeptidase - 9 (MMP - 9), Bladder Cancer - Associated Protein (BLCA - 4),Toll - Like Receptors (TLR - 2and TL - R4) level among them and to evaluate their roles in cancer development.One hundred thirty seven Iraqi individual were divided to 28(20.43%) newly diagnosed and 29(21.16%) recurrent bladder cancer patients (relapse), 40(29.19%) apparently healthy volunteers and 40(29.19%) autopsies (apparently normal urothelium), of whom urinesample and tissue biopsy were collected, clinical diagnosis of patients carried out by cystoscopic and histopathological examination, the mean ±SD age of bladder cancer patients were (63± 9.3) with (M : F ratio7.1 : 1).Predominant cancer type was Transitional cell carcinoma (TCC). According to risk factors of bladder cancer, out of 57 bladder cancer patients, 34(59.64%), 29(50.87%), 9(15.78%), 7(12.28%), 6(10.52%) were smoker, had UTI, history of Schistosomiasis, family history ofcancer and stones respectively. In this study 30 patients had non - muscle invasive bladder cancer, most of them (21) had newly diagnosed tumors, and only 9 had recurrent disease, as well as, 27 patients with muscle - invasive bladder tumor, just 7 had newly diagnosed tumors and 20 with recurrent disease.According to the result of ELISA technique, the mean±SD urine level IL - 8(pg/ml) for recurrent bladder cancer patients was 359.6±170.1pg/ml, for newly diagnosed was 265.95±139.09pg/ml and for healthy volunteers was 62.04±37.66pg/ml. The mean ±SD concentration of urine MMP - 9(pg/ml) was 7368.3±1730.19pg/ml for recurrent, 6176.8±2366.9 pg/ml for newly diagnosed and 1131.53±1554.80 pg/ml for healthy volunteers. Mean±SD Level of urine BLCA - 4 (ng/ml) for recurrent was 1.45± 0.26 ng/ml, for newly diagnosed was 1.30± 0.22 ng/ml and for healthy volunteers was 1.02±0.067 ng/ml. Urine level of these markers was significantly higher in recurrence group when compared with newly diagnosed and these levels decreased in normal volunteers which was statistically significance (P<0.001 for IL - 8, MMP - 9and BLCA - 4),also there was a significant increase in urine IL - 8 level according to grade(P=0.0002) and muscle invasion(P= 0.0009) as well as BLCA - 4 showed this significant increase in high grade(P=0.0001), and muscle invasion(P=0.0001),but no significant difference was found in the level of urine MMP - 9 with grade(P=0.23) and muscle invasion(P =0.069)In comparison, IL - 8 and MMP - 9 IHC staining of bladder tissue, showed low expression in cancerous tissue with no significant difference between cancer and normal urothelium(P=0.140 for IL - 8, P=0.265 for MMP - 9 ), and unrelated to grade, muscle invasion and recurrence.Significant increase in TLR - 2 and TLR - 4 expression in bladder cancer tissue than in normal urothelium (P=0.0001 for each), and according to grade and muscle invasion, TLR - 2 showed significant over expression in high grade than low grade (40.7%vs36.6%) with P=0.018, muscle invasion than non - muscle invasion (44.4%vs33.3%) with P value of 0.02, while TLR - 4 was none significantly correlated with grade andmuscle invasion. As well as, there was no correlation between these receptors with tumor recurrence.In regard to risk factors, Smoking, schistosomiasis and family history showed correlation with study marker in different manner as, IL - 8 was significantly highly expressed in smoking associated bladder cancer group, as well as patients with family history of bladder cancer showed high expression IL - 8, for Schistosoma associated TCC patients and UTI they demonstrated a statistically significant high expression of TLR - 2 p= (0.0001).From this study we conclude that urine IL - 8, MMP - 9and BLCA - 4 measured by ELISA showed specificity in diagnosis of bladder cancer, besides that, urine IL - 8, MMP - 9 and BLCA - 4 have a role in discrimination between newly diagnosed vs recurrent, with a significant association between urine IL - 8 with BLCA - 4 (P= 0.0001) and IL - 8 with MMP - 9 (P= 0.005) in patients with recurrent bladder cancer. Urine IL - 8 and BLCA - 4 concentration were statistically with significant increase in high grade than low grade and muscle invasion than non - muscle invasion, On the other hand, bladder cancer cells over express TLR - 2 and TLR - 4,while TLR - 2 showed correlation with high grade and muscle invasion,TLR4 did not show such correlation. Lastly, IL - 8 and MMP - 9 staining showed low expression in tumor tissue of different grades, stages and groups.
