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تقييم التعبير الجيني للجينات CK19, MGB, MUC1 microRNA - 195 and microRNA - let 7a في نساء عراقيات مصابات بسرطان الثدي == Evaluation of MGB1, CK19, MUC1, microRNA - 195 and microRNA - let - 7a Expression In Iraqi Women With Breast Cancer
Author name:
جودت نوري غائب
Supervisor name:
عبد الحسين مويت الفيصل
General topic:
Biology
Specific topic:
Biotechnologies
Degree:
Doctorate
University:
University of Baghdad - Institute Of Genetic Engineering And Biotechnology - Department Of Biotechnology
Language:
English
University location:
Baghdad
First pages:
24T2730 - p.pdf
Abstract:
The present study aimed to shed light on the identification a panel of genes with distinct expression patterns in breast cancer patients as a useful tool for breast cancer early detection and progression. The present study designed to investigate the levels of genes expression of five genes panel (MGB1, CK19, MUC1, miR - let7a, and miR - 195) in circulating free mRNA and miRNA from blood of breast cancer patients versus noncancerous samples (benign tumor and healthy controls) to establish a biomarker panel potentially useful for early detection and progression of disease. The expression patterns of the identified genes were then compared with certain clinical features (age, lymph node status, and tumour size).Blood samples from 55 patients with different stages of newly diagnosed invasive ductal carcinoma were provided by certain Iraqi hospitals. Two control groups were used in this study; 10 samples of patients with benign breast tumors, and 20 samples from healthy donors. The samples preservation with TRIzol was done. Samples subjected to total RNA extraction, and then molecular study by using reverse transcription and real time PCR at Molecular Oncology Unit in Guy´s Hospital - Kings College / London.The study reached the following results : 1. The patients’ age range was 24 - 70 years and the median was 49 years with high frequency of patients in the range of 40 - 59 years. According to the family history, 50(90.91%) of patients were have negative family history. According to the clincopathological features (lymph node status and tumor size) the percentages of patients with multiple lymph nodes and tumor size 2.0 - 2.9 cm were the highest groups, which showed statistically highsignificant differences.2. For MGB1 gene expression, the result showed that 30(54.5%) patients were MGB1 - positive while 25(45.4%) patients were MGB1 - negative.According to malignancy status the percentage of patients with high level of MGB1 gene expression 22(40%) was significantly high. In correlation with age groups there was statistically no significant differences in the levels of gene expression with age. In correlation with clincopathological features, lymph node status showed that the highest percentage of MGB1 positive patients 18(66%) were multiple for lymph node status, and the tumor size results showed that there was decreasing in the MGB1 geneexpression with increasing of tumor size. 3. For CK19 the results of present study showed that 41(74.54%) patients were CK19 - positive, while 14(25.46%) patients were CK19 - negative.According to malignancy status the percentage of patients with high level of CK19 gene expression 30(54.45%) was significantly higher in compare with benign tumor patients and healthy controls. In correlation with age groups there was statistically no significant differences in the levels of gene expression with age. In correlation to the clincopathological features, lymph node status results showed that the highest percentage of CK19 positive patients 24(88.89%) were multiple for lymph node status, and there was increasing in the CK19 gene expression with increasing of tumor size.4. Mucin 1 (MUC1) gene expression results showed that the percentage of MUC1 - positive breast cancer patients 72.73%(n=40) was significantly higher when compared with benign tumor patients and healthy controls. According to the age groups the results showed no significant correlation with patients age groups. The clincopathological features results showed that the highest percentage of MUC1 positive patients 84.21%(n=16) have few lymph node status, and there was statistically significant association between the increasing of MUC1 gene expression and tumor size. 5. The miR - 195 gene expression results showed that the percentage of patients with positive miR - 195 gene expression 83.64%(n=46) was significantly higher than patients with negative miR - 195 expression 16.36%, the study also showed that the percentage of high miR - 195 expression samples 69.09% (n = 38) was significantly higher in compare with benign tumor patients and healthy controls. According to the clincopathological features, patients with multiple and few lymph node metastasis were found to have significantly the highest percentages of miR - 195 expression, while the tumor size results showed that there was increasing in the miR - 195 gene expression with increasing of tumor size. 6. The percentage of miR - let 7a - positive breast cancer patients 81.82% was significantly higher, when compared with miR - let 7a - negative patients 18.18%. In correlation to the clincopathological features, results showed no significant correlation in miR - let7a gene expression levels with patients age groups, for lymph node status, the results showed that the highest percentages of let 7a positive patients were those with multiple lymph node and few lymph node metastasis. The tumor size results showed that there was increasing in miR - let 7a gene expression with increasing of tumor size.7. According to genes combinations, three genes combination (CK19, miR - 195 and miR - let 7a) was significantly positively expressed with percentage of 60%(33/55), which reflect their potential diagnostic and prognostic value.8. The study concluded that the three genes combination (CK19, miR - 195 and miR - let 7a) may have potential applications as a diagnostic and prognostic markers for breast cancer.
