الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 173 |  |  |
| | | from | 173 | | |
Abstract
The present study was designed to investigate the role of both TRIM59 and TIGAR in CRC in comparison to benign colonic lesion tissues and normal intestinal tissue from the safety margin around the tumor. Also, to estimate p-Akt, p53, GSH and MDA in the same groups.
Sixty patients diagnosed with CRC and sixty patients with benign lesions were recruited for the present study. The study included 180 samples classified into 3 groups: group (1) include 60 tumor tissue samples from CRC patients taken from the excised tumor mass of colorectal cancer patients. Safety margins around the tumor, considered as a group (2) that include 60 normal intestinal tissue samples (5cm from the tumor). group (3) include 60 diseased intestinal tissue samples from high risk patients (including those with IBD, adenoma, or familial polyposis).
The study was done on 28 males and 32 females patients in the CRC group, and in the benign group 37 males and 23 females with no significant difference. The mean age of the cancer group was 41.97±1.61 years while that of benign patients was 40.23±1.27 years with no significant difference.
TRIM59 and TIGAR mRNA expression were measured using quantitative real-time polymerase chain reaction qRT-PCR. Their protein levels were estimated by ELISA assay. Phospho-Akt expression was detected by using ELISA assay. P53 expression was done using immunohistochemistry. GSH and MDA levels were measured using colorimetric kits. The results obtained were statistically analyzed by suitable techniques.
The results of the present study showed that both mRNA expression and protein levels of TRIM59 and TIGAR together with MDA tissue level were significantly higher in the CRC tissues compared to the control group and to benign lesions and significantly associated with TNM staging and positive lymph node metastasis. Their levels also were significantly higher in benign lesions than the control group.
Moreover, TIGAR protein levels were significantly associated with the site of the tumor, the highest level was in the colon. There was also a significant association between TIGAR protein levels and type of tumor pathology.
The p-Akt level was significantly highly expressed in the CRC tissues compared to benign lesions and control group, it showed also significant high expression in benign lesions group in comparison to control group.
The study also determined the level of GSH and MDA. It showed that GSH levels were significantly low in CRC tissues compared to benign and normal tissues, and its highest levels were in benign lesions with significant difference in comparison to the control group. MDA levels were significantly higher in CRC and benign lesions in comparison to the control group. Its level in CRC was also significantly higher than that in benign group.
In the benign lesion group, there were a significant high expression of TRIM 59 gene and protein levels and low GSH levels in benign inflammatory bowel precancerous lesions compared to non-inflammatory precancerous lesions.
The current results showed that both tissue TRIM59 protein and mRNA expression correlate significantly with high MDA and low GSH in benign lesions. There was a significant positive correlation between tissue TRIM59 mRNA expression and its protein levels with MDA in CRC and also between TIGAR protein levels and MDA in CRC tissues. There was also a significant positive correlation between cancer tissues TRIM 59 and TIGAR mRNA expression and between their protein levels.
Immunohistochemical detection for expression of P53 in different studied groups documented, Score 0:>5% positive cells (control). Score 1: 5-25% positive cells (ulcerative colitis). Score 2: 25- 75% positive cells (adenoma). Score 3: <75% positive cells (Colorectal cancer).