MicroRNAs as Possible Biomarkers for Breast Cancer in Samples of Iraqi and British Women

number: 
3309
إنجليزية
Degree: 
Author: 
Zaynab Saad Abdul-Ghany
Supervisor: 
Dr.Hameed M.Jasim
Dr. Nahi Y. Yassen
year: 
2014

This study aimed to determine the expression of microRNA molecules as early prognosis biomarkers for the detection of breast cancer. To achieve this project, a total of fifteen serum samples were collected from Iraqi women with breast cancer and from six serum samples were collected from healthy women volunteers as a control group. In these samples, levels of estrogen and progesterone hormones and cancer antigen 15-3 (CA15-3) marker were determined to study the relationship between these parameters and breast cancer in Iraqi women.  Results showed that there is a significant negative correlation

(r2 =¯0.4) between the level of serum estrogen hormone and the age of breast cancer patients, while there is no significant correlation between the level of progesterone hormone and the age of the patients, as well as no significant correlation between the level of CA15-3 marker and patients age in comparison with healthy controls which means that estrogen hormone level was decreased with the age of atients.
On the other hand, the expression of several microRNAs in serum samples of breast cancer women and healthy controls were examined by using qPCR technique. These microRNAs included let-7a, miR-21, miR-222, miR-205, miR218, miR-378, miR-15b, miR-26b, miR-27a, miR-429, miR-34a, miR-34b and miR-191(as endogenous control). Results showed that there is a significant increase (P<0.05) in the expression of let-7a and miR-21 in serum breast cancer patients in comparison with normal healthy controls with fold change (2.1 and 3.5) respectively, while there is significant downregulation (P<0.05) in the
expression of miR-26b and miR-429 in serum of breast cancer patients compared with healthy volunteers with fold change (0.5) for both miRNAs that be regarded as novels miRNAs in detection of breast cancer. The rest of miRNAs did not show any significant variation on their expression in serum breast cancer patients and healthy women. The expressions of miRNAs were also studied in thirteen plasma samples of British women with breast cancer and eight healthy normal volunteers. Results showed that there is a significant increase (P<0.05) in the expression of let-7a and miR-26b in plasma samples of breast cancer women compared with plasma of healthy women with fold change (1.5 and 2.0) respectively, while the expression of miR-27a and miR-222 were significantly down regulated (P<0.05) with fold change of (0.6) for both miRNAs.On the other hand thirteen of matched British breast cancer tissues and non-cancerous tissues were used to determine the expression of miRNAs. The results revealed that miR-21 and miR-429 (the novel) were significantly increased (P<0.05) expression in breast cancer tissues compared to normal noncancerous tissues with fold change (4 and 14) respectively, however significant downregulation (P<0.05) of miR-378 and miR-26b (the novel) expression has been detected in breast cancer tissues with fold change (0.2 and 0.6) respectively compared to its matched healthy normal non-cancerous breast tissues. The last part of this study determined the expression of apoptotic genes in British breast cancer tissue samples and its matched non-cancerous normal breast tissues. These apoptotic genes included in this study are P53, P21, Bax, Bcl2, BRCA2 and TWIST genes. Results indicated that the expression of P53, P21 and TWIST were significantly downregulated (P<0.05) in breast cancer tissues compared to non-cancerous breast tissues with fold change 0.9, 1.0 and 1.0 respectively, while there is a significant upregulation (P<0.05) in the expression of Bax and BRCA2 with fold change 3.5 and 20.0 respectively. In conclusion, the results indicated that there is a possibility of detection the changes in the level of microRNAs expression as useful biomarkers for the detection and early diagnosis of breast cancer.