Search In this Thesis
   Search In this Thesis  
العنوان
Evaluation of Cell-Free Circulating Plasma
DNA in Prostate Cancer /
المؤلف
Nofal,Nagwa Mamdouh.
هيئة الاعداد
باحث / Nagwa Mamdouh Nofal
مشرف / Karima Mohammad Sweify
مشرف / Amal Fawzy Said
مشرف / Hany Mohammad ElFayoumy
تاريخ النشر
2017
عدد الصفحات
149p.;
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
Molecular Biology
تاريخ الإجازة
1/1/2017
مكان الإجازة
جامعة عين شمس - كلية البنات - علم الحيوان
الفهرس
Only 14 pages are availabe for public view

from 149

from 149

Abstract

Prostate cancer (PC) is a common health problem. It starts to develop at the age 50 years, the highest level reaching at 60 – 70 years of age. The highest incidence is recorded in US and Canada, followed by European countries, then the Asian population and the lowest incidence is in Arabic populations.
Prostate gland secretes prostatic specific antigen (PSA) into the semen and the blood stream. The elevated plasma PSA is occurred in PC, though it is widely used for diagnosis the tumor in patient. However, PSA levels may elevate in the prostatic disease, so it was replaced by the measurement of CF-DNA which has received increasing attention as a cancer biomarker. Therefore, the objective of the study was to evaluate CF-DNA in plasma of PC patients comparing to that found in BPH patients and that detected in healthy men. In addition CF-DNA levels were analyzed in relation to the clinicopathological characteristic of the studied cases.
The study was performed at National Cancer Research (NCI) Cairo University and the Urology department Qasr El-Aini between October 2013 to June 2015. The study included 105 Egyptian men classified into three groups. The 50 men with PC, 25 men with BPH were obtained from urology department at Qasr El-Aini Cairo University. The pathological and clinical staging information was obtained from the hospital charts. In addition 30 control subjects were involved. The current laboratory investigations were:
a) Tumor markers tPSA and f/t PSA ratio.
b) Measurement of DNA concentration
c) Q RT-PCR using two primers ALU115 and ALU247 with SYBR green as fluorescent stain.
Blood samples were collected from the studied individuals. Serum and / or plasma was separated and frozen at 20oc until analysis time the serum was used for determination of t PSA and FPSA. DNA was extracted from the plasma. The levels of CFDNA were measured through QRT-PCR technique all of the studied patients were subjected to, full history, complete clinical examination prostate biopsy for histopathological examination bone scan for detection metastasis. Tumor size, Gleason score tumor grade. The results could be summarized in the following:
As for t PSA concentration and f/t PSA ratio, the concentration of t PSA and f PSA were elevated in PC patients than the other studied groups. So, significant difference was obtained between the three studied individuals. The levels of CF-DNA produced by ALU115 and / or ALU247 and its integrity were higher in PC patients than that of BPH. Statistically the difference was significant comparing to control.
No association was found between the level of CF-DNA and the clinico-pathological findings (e. g. Gleason score, t PSA, f/t PSA ratio).
Comparing between the level of CF-DNA produced by ALU115 and / or 247 in metastatic and non-metastatic specimen, the median were found to be 662.9, 167.96 and 187.9, 54.5 for metastatic and non-metastatic respectively. Statically significant differences were obtained between the two studied samples. The same was detected for the integrity. ROC curve was done to obtain the sensitivity against the false positive rate (1 – specificity to obtain the differences between metastatic & non-metastatic cases).
The sensitivity was 96.4, 92.9 for 115 and ALU247 respectively. The specificity was 86.4 & 72.7 while the integrity was 64.3 and 63.6 for sensitivity and specificity. The areas under the curve were 0.981, 0.934 and 0.657 for ALU115, ALU247 and integrity respectively.
The present results revealed highly significant levels of CFDNA and its integrity in plasma obtained from ALU115 and/or 247 in PC patients compared to patients with BPH. Moreover, significant differences in CFDNA levels and its integrity in metastatic patients in relation to patients with non-metastatic tumors were recorded.
However, the results obtained from ALU115 were significantly higher than that of ALU247.
Therefore, based on the present results and the previous published works, the CFDNA assay may be a valuable technique for screening and monitoring metastasis in cancer patients as it provides a simple and inexpensive measure for cancer detection.
Further studies on a large number of PC patients are needed to confirm the obtained conclusions.