الفهرس 
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Abstract
Ovarian cancer) OC) is the most aggressive of all gynecological malignancies and is the leading cause of cancer-related deaths among females worldwide, and has the highest mortality rate and the poorest prognosis among gynecological malignancies. The number of cases is steadily increasing worldwide. Nowadays, even with the advances in its treatment, including surgery, chemotherapy, and radiotherapy, survival rates remain poor for the majority of patients. Ovarian cancer is often asymptomatic in the early stages; therefore, it is considered a silent killer. The signs and symptoms become more apparent as cancer advances. It will also be important to establish tumour markers that could be used to diagnose cancer in the early stages in order to improve the survival of these women.
This study includes 120 patients with ovarian cancer classified into three groups: benign, early and late (each group contains 40 women) together with 30 healthy control subjects. Patients will be selected from those attending the inpatient of Oncology Unit at the Gynecology and Obstetrics Hospital, Ain Shams University Educational Hospitals (El Demerdash Hospital), Cairo, Egypt.
Blood samples were collected before surgery and divided into special tubes to separate serum or plasma, stored at -20 0C to be thawed only once on demand for determination of biochemical investigations.
All samples were analyzed for determination of microRNA-204 by qRT-PCR technique and Serum levels of Hepcidin, Microfibril-associated glycoprotein 2 (MAGP2), Ferroportin, CA125 and CA19.9 were measured using ELISA technique. The levels of complete blood count (CBC), Liver function tests (ALT and AST), creatinine, Prothrombin time (PT), partial thromboplastin time (PTT) and International Normalized Ratio (INR) were also analyzed.
The aim of this study is to find better early non-surgical indicators of high sensitivity and specificity and to achieve positive predictive value for the early detection of ovarian cancer. A combination of vital indicators microRNA-204, CA125, and CA19.9 can also provide successful early detection of ovarian cancer and ultimately improve patient outcomes.
The results of the present study were clearly indicated that:
Results of CBC showed a significant decrease in lymphocytes in all patient’s groups while a significant increase was observed in platelets in early ovarian cancer patients when compared with the control group.
A highly significant decreases in ALT were observed in all patient’s groups and AST data revealed, non-significant changes in all patient’s groups of ovarian cancer when compared with control group. Creatinine recording highly significant increases in benign ovarian tumour and late patients of ovarian cancer.
A highly significant increase in PT were observed in early ovarian cancer patients. PTT provided highly significant increases in all patient’s groups when compared with control group. INR showed a significant increase in early ovarian cancer group of patients when compared with the control group.
CA125 lacks sensitivity and specificity and, hence, is not useful as a single biomarker for the early diagnosis of ovarian cancer.
The ROC curves for hepcidin, MAGP2, and FPN1 indicated that they were weak diagnostic markers for ovarian cancer.
MicroRNA-204 showed highest diagnostic performance for early and late ovarian cancer patients, thus, micro-RNA-204 is a better biomarker than the other microRNAs and may serve as a useful biomarker for detecting ovarian carcinoma.
The AUC increased when CA125 was combined with microRNA-204 and CA19.9. Thus, microRNA-204 and CA19.9 combined with CA125 predict ovarian carcinoma better than any marker alone.
In the benign group of patients with ovarian tumors, a significant weak positive correlation was observed between microRNA-204 & Hepcidin. But there was a significant weak negative correlation between microRNA-204 & Ferroportin. On the other hand, there was a highly significantly moderate positive correlation was observed between MAGP2 & CA125.
In the early group of ovarian cancer patients, a significant weak positive correlation was shown between MAGP2 & CA19.9
In the late group of patients with ovarian cancer, a highly significantly moderate positive correlation was shown between MAGP2 & Ferroportin and between CA125 & CA19.9 and a significant weak positive correlation was observed between Ferroportin & Hepcidin and between Ferroportin & CA125.
Sensitivities and specificities of microRNA-204, CA125, and CA19.9 were extremely high and the positive predictivities (the ability of the test to correctly predict the presence of disease with the help of Bayes’ rule) for ovarian cancer were above 50 percent. Thus, these biomarkers are good diagnostic tools for diagnosing ovarian cancer and very good at ruling out the disease. Thus, good sensitivity and specificity constitute a good diagnostic test.
Conclusion:
Combination of microRNA-204, CA125 and CA19.9 is very important diagnostic biomarkers significantly associated with ovarian cancer disease and must be used as a strongest predictor for early detection of ovarian cancer, so they must be involved in the routine checkup of Egyptian ovarian cancer patients for monitoring the disease progression.