University of Khartoum

Identification and Characterization of Urinary Micro-peptides as Potential Biomarkers for early Detection of Ovarian Cancer among Sudanese women

Identification and Characterization of Urinary Micro-peptides as Potential Biomarkers for early Detection of Ovarian Cancer among Sudanese women

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Title: Identification and Characterization of Urinary Micro-peptides as Potential Biomarkers for early Detection of Ovarian Cancer among Sudanese women
Author: Murgan, Sulafa SeifEldin Adam
Abstract: Introduction: Ovarian Cancer is the second major lethal gynecologic malignancy in Sudanese Women. Most cases present late due to the silent signs of the disease.Moreover, the low diagnostic sensitivity and specificity of CA125 antigen as a biomarker for ovarian cancer make early diagnosis a challenging task. Proteomics and peptidomics have been used as biomarkers for the diagnosis of many cancers and diseases. This study aims to test urinary micro-peptides as potential diagnostic biomarkers for the early diagnosis of ovarian cancer. Materials and methods: This is a longitudinal, analytical and hospital-based study that was conducted over two years in Greater Khartoum State, Sudan, centres included: Omdurman Military Hospital and Khartoum Radiation & Isotopes Centre. Following informed consent, urine, plasma and ascitic fluid samples were collected from 112 women with histologically proven ovarian cancer were enrolled. Ascitic fluid was taken by physician from the patients with advanced stage of ovarian serous adenocarcinoma for cytology. Two hundredapparently healthy age-matched female comparators were also enrolled. Follow-up was done every 6 months for a total of two years after removal of ovaries and chemotherapy. Plasma CA125 antigen was measured using ELISA.SDS-PAGE was used to determinedurinary micro-peptides. Selected urinepeptides were sequenced using Edman degradation technique. Results: The overall mean age of patients 46.5±27.5, while that of the female comparators was 42.5±22.5. More than forty percent (50/112, 44.6%) of the patients developed symptoms of abdominal discomfort, pelvic pain and irregular bleeding during the last6 months before presentation. Thirty four percent weredeveloped symptoms within one year, 5.4% (6/112) and 14.3% (16/112) developed symptoms within two and three years respectively. A third (43/112, 38.4%) was single, 41.1% (46/112) were married and had no children and 20.5% (23/112) were married and had children. Co-cancers were seen in the minority (5.4%, 6/112). Serous adenocarcinoma was seen in the majority (81.1%, 91/112) of patients,with stages III and IV in 39.6% and 33% of patients respectively. A quarter (24.1%) was seen at stage II. A minority (3.3%) was diagnosed earlyat stage I.The mucinous type was seen in 9.8% of patients (11/112), with 18.2% at stageII, 45.5% at stageIII and 36.45% at stage IV. Theendometroid type was seen in 10.7% (6/112) of patients with 3.6% at stage, 1.8% at stageIII. A minority was reported as germinoma (1/112, 0.8%), and poorly differentiated carcinoma as (3/112, 2.7%). CA125 antigen was detected in the plasma of less than a quarter (23.2%) of patients, and were not detected and in comparators (p=0000). Protein bands of sizes15kDa, 35kDa and 45kDa were detectedinthe patient’s urine samples but not detected in the urine of healthy comparators (p=0000). The protein band size 15kDa was detected in 42.9% (48/112) of the patients, while the 44kDa was seen in 24.1% (27/112). The 45 kDa protein band was detected in 16.1% (18/112) of the patients. More than third of the patients (42/112, 37.5%) showed no micro-peptide urinary bands. The 6 months follow up showed only the 45kDa protein band in 10% of patients. These proteins were sequenced and identified as: 45kDa= CAT (Catalase), 35kDa= AAG (alpha-1 acid glycoprotein), and 15kDa= Prxn2 (Peroxiredoxin2). Conclusion: Urinary micro-peptides [Catalse, alpha-1 acid glycoprotein and Peroxiredoxin] can form the basis of a non-invasive, simple, sensitive and specific for early diagnosis of ovarian cancer.
URI: http://khartoumspace.uofk.edu/123456789/26487


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