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العنوان
The role of circulating cell-free DNA and its Integrity using ALU (247/115) bP sequences as a biomarker for diagnosis of breast cancer /
المؤلف
Hussein, Fatma Mostafa Mohammed.
هيئة الاعداد
باحث / فاطمة مصطفي محمد حسين
مشرف / هبة أحمد عبدالحفيظ
مناقش / حنان عمر محمد
مناقش / محمد زكريا عبدالرحمن
الموضوع
Breast cancer
تاريخ النشر
2023.
عدد الصفحات
129 p. ;
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الوراثة (السريرية)
الناشر
تاريخ الإجازة
5/3/2023
مكان الإجازة
جامعة أسيوط - كلية الطب - Clinical Pathology
الفهرس
Only 14 pages are availabe for public view

from 208

from 208

Abstract

This study was conducted on 60 newly diagnosed breast cancer patients, aged 30-70 years. They were classified according to TNM staging system into 8 (stage I), 27 (stage II), 21 (stage III) and 4 (stage IV). The study also included 20 patients with benign breast lesions, of which; 10 patients with breast abcess, 4patients with fibroadenosis, 3patients with mastitis, 2 patient with duct ectazia 1patient with macroamastia. All patients were recruited from General Surgery Department, Assiut University Hospital and Surgical Oncology Department, South Egypt Cancer Institute, Assiut University. The study also included 20 age matched apparently healthy individuals who were selected as a control group for comparison. Practical work was carried out at Clinical Pathology Department, Assiut University Hospital. All participants were subjected to the following: Full medical history. Full clinical examination. The following investigations were done for patients only as appropriately indicated: Chest x-ray. Abdominal ultrasound. Breast ultrasound or mammography. Histopathological examination of breast mass specimens (Tru cut or fine needle aspiration cytology). MRI and Bone scan.Laboratory investigations for all participants: Routine laboratory investigations: Hematological investigations: - Complete blood count (CBC). - Prothrombin time, concentration & international normalization ratio (INR). Chemical investigations: - Random serum glucose. - Kidney function tests. - Liver function tests. - Calcium. Special laboratory investigations: - Serum carcinoembryonic antigen (CEA). - Serum cancer antigen 15-3 (CA15.3). Both were done by chemiluminescence immunoassay. - CfDNA concentration and integrity in serum samples were examined by measuring ALU repeats (ALU-115 bp, ALU-247 bp) by quantitative real-time polymerase chain reaction (q-PCR). The current study showed the following findings: CEA, CA15.3, ALU-115, ALU 247, and DNA integrity among studied groups: Regarding CEA no statistically significant difference was found between different groups. The patients with breast cancer had statistical significantly higher level of CA 15.3 in comparison to those with control group. It was found that patients with breast cancer and had statistically significant higher ALU115 in comparison to the control group. Regarding ALU 247 value It was found that both breast cancer group and those with benign breast lesions had statistically significant higher ALU247 and DNA integrity in comparison to the control group. CEA, CA15.3, ALU 115, ALU 247 and DNA integrity based on breast cancer stage: It was found that patients with early stage of breast cancer (group 3A) had statistically significant higher CEA and CA 15.3 level in comparison to those with benign lesions and control group. Also, it was found that, group2, group3A and group3B had statistically significant higher level of ALU 115, ALU 247 and DNA integrity in comparison to group1. Correlation between BC biomarkers in patients groups: In control group (group 1): Both CEA and CA15.3 revealed statistically significant positive correlation. Also DNA integrity and CA15.3 revealed statistically significant positive correlation. DNA integrity and ALU 115 revealed statistically significant negative correlation. While DNA integrity and ALU 247 revealed statistically significant positive correlation. In benign cases (group2): Both CEA and CA15.3 revealed significant positive correlation. ALU 115 and ALU 247 revealed significant positive correlation. While DNA integrity and ALU 247 revealed significant positive correlation. In early stages of breast cancer cases (stage I, II) (group 3A): Both CEA and CA15.3 revealed significant positive correlation. The ALU115 and CA 15.3 revealed statistically significant positive correlation. The ALU247 and ALU 115 revealed statistically significant positive correlation. The DNA integrity and ALU115 revealed statistically significant negative correlation. While DNA integrity and ALU 247 revealed statistically significant positive correlation. Advanced stages of breast cancer (stages III, IV) (group 3B) Both CEA and CA15.3 revealed statistically significant positive correlation. ALU 115 and ALU 247 revealed statistically significant positive correlation. Also DNA integrity and ALU 247 revealed statistically significant positive correlation. Diagnostic performance of BC biomarkers for malignant cases (Control VS malignant Cases): In this study, we constructed ROC curve for diagnosis of BC vs. healthy controls. Serum CEA was 66.8% sensitive and 55 % specific for with AUC of 0.638. CA15.3 was 70% sensitive and 55% specific with AUC of 0.677. Serum ALU 115 was 75 % sensitive and 65 % specific with area AUC of 0.730. ALU 247 was 86.7 % sensitive and 75% specific with AUC of 0.850. DNA integrity was 70% sensitive and 60 % specific with AUC of 0.710. Diagnostic performance of BC biomarkers (Early BC vs. Control): In order to early detect BC, we constructed ROC curve for diagnosis of early BC (TNM stages I & II) vs. healthy controls. Serum CEA was 62.8 % sensitive and 85 % specific with AU) of 0.703. CA15.3 was 71.4 % sensitive and 55% specific with AUC of 0.701. Serum ALU 115 was 80 % sensitive and 65 % specific AUC of 0.739. ALU 247 was 88.6% sensitive and 75% specific with AUC of 0.857. DNA integrity was 68.6 % sensitive and 60 % specific for AUC of 0.719.