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العنوان
Expression of the matrix metalloproteinase regulator- RECK-and its clinical significance in breast cancer /
المؤلف
Ahmed, Manar Fouad.
هيئة الاعداد
باحث / Manar Fouad Ahmed
مشرف / Azza Hassan AbouGhalia
مشرف / Hussein Abd Aleem Boshnak
مشرف / Eman khairy Farahat
تاريخ النشر
2016.
عدد الصفحات
166 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
1/1/2016
مكان الإجازة
جامعة عين شمس - كلية الطب - Medical Biochemistry and Molecular Biology
الفهرس
Only 14 pages are availabe for public view

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from 166

Abstract

Breast cancer is the most common cancer worldwide in females, and the 2nd most common cancer overall (Ferlay et al., 2013). The reversion inducing cysteine rich protein with kazal motifs (RECK), inhibits secretion and enzymatic activity of MMP-2, and MMP-9, membrane type 1 matrix metalloproteinase (MMP-14). Down-regulation of RECK has been implicated in many tumors. Thus expression of RECK gene is considered to be an adequate prognostic biomarker for patients diagnosed with various tumors (Noda and Takahashi, 2007).

This study was carried out at Medical Biochemistry and Molecular Biology Department, in collaboration with General and Plastic Surgery Departments, Faculty of Medicine, Ain Shams University. The study was approved by Research Ethics Committee (REC), Faculty of Medicine, Ain Shams University.
The study included 60 female patients classified into two groups:
• group A: Consisted of twenty three female patients with histopathologically confirmed malignant breast tumors. Patients with previous history of radiotherapy, systemic chemotherapy, or with malignancy other than breast cancer were excluded from this study. Breast cancer patients underwent either radical mastectomy or modified radical mastectomy. Breast tissue specimen from suspected lesions were examined histopathologically and clinical staging according to TNM classification was performed (AJCC, 2010).
• group B: Consisted of thirty seven Egyptian females who underwent breast reduction as a control group. They were recruited from Plastic Surgery Department, Faculty of Medicine, Ain Shams University.
The aim of the present study was to evaluate the clinical significance of RECK gene expression in patients with breast cancer in relation to clinicopathological factors. To achieve this goal we measured RECK expression both at transcription and translation levels using RT-qPCR and ELISA respectively in tissues and sera - for first time- of breast cancer patients and control group.
The present study demonstrated the following:
• Both RECK mRNA and RECK protein were significantly lower in sera and breast tissue specimens in breast cancer patients than the control group which may suggest a role of RECK gene in breast cancer pathogenesis.
• Correlation between RECK gene expression and the different clinicopathological criteria in the patient group revealed the following:
- Higher RECK gene expression in breast tissue specimens from obtained from premenopausal women and OCP users may suggest a link between these hormones and expression of RECK gene.
- Higher RECK gene expression in breast tissue specimens obtained from patients with negative lymph node metastasis supports the role of RECK gene in suppressing metastasis.
- High level of RECK protein in patients with invasive lobular carcinoma needs further estimation on larger number of samples from this specific tumor type.
• The best cutoff values for RECK protein in serum and breast tissue samples were 2.55 ng/ml and 33.9 pg/µg protein, respectively. The corresponding sensitivities and specificities were 60.8%, 70.5% in serum and 86.4%, 66.7% in tissue.
• The best cutoff values for RECK mRNA were 0.32 and 0.72 in serum and tissue, respectively. At these cutoff values the sensitivities and specificities were 100%, 100% in serum and 100%, 85.7% in tissue.
• There was statistically significant correlation between RECK mRNA (or protein) in tissue and serum (P< 0.05( samples obtained from the same patient.
In conclusion; we recommend
• The use of serum as – a non invasive tool – rather than tissue specimen to investigate the expression of RECK gene in breast cancer. Also, to gain higher sensitivity and specificity it is better to measure RECK mRNA than RECK protein.
• Further studies are needed to discover drugs that activate RECK gene aiming for prevention of breast cancer in high risk women or enhancing other chemotherapeutics in patients with breast cancer.