ctDNA Methylation for Detecting Ovarian Cancer

Study Overview
=================
Brief Summary
-----------------
Ovarian cancer is one of the most dangerous and leading gynecological cancer, with significant cancer-related mortality among women. However, current detection methods are still limited, with approximately 70% of patients with high-grade serous ovarian cancer often being advanced at the initial diagnosis and more than 80% with intraperitoneal spread. The five-year survival rate for late detection is only 29%; on the contrary, if detected early, the five-year survival rate can reach 92%. Therefore, early diagnosis and detection are essential in diagnosing and treating ovarian cancer. Liquid biopsy has attracted widespread attention because of its non-invasive, real-time, and dynamic characteristics. Cell-free DNA in plasma can identify a small tumor burden well and reflect the clinical cancer information of cells.The role of hypermethylation in developing malignant tumors has received increasing attention. Methylation is one of epigenetics and plays a vital role in the occurrence and development of tumors. According to previous research basis of the researchers, it has been found that CDO1 and HOXA9 genes show hypermethylation in ovarian cancer, and they are considered one of the biomarkers for detection. Therefore, this study will further explore the detection of CDO1 and HOXA9 methylation levels based on cell-free DNA in blood and compared with ovarian pathology results; the application of methylation detection technology in ovarian cancer/precancerous lesions will further explore the application value of non-invasive diagnosis and prognostic follow-up.This study will involve three centers and is expected to enroll more than 1,400 clinical subjects, further examine the consistency of methylation detection kits with the histopathological examination, ROMA index, and Sanger sequencing results, and obtain sensitivity and specificity technical performance parameters.

Detailed Description
-----------------
This study has two phases: the Clinical Performance Validation cohort and the Assay Accuracy Verification cohort. The  Clinical Performance Validation phase of this study will assess the reagents to detect plasma samples; patients undergo routine examinations by clinical trial institutions, including but not limited to tumor markers and histopathological examinations. The clinical performance of the assessment reagents was systematically evaluated by evaluating the consistency between the test results of the assessment reagents and the histopathological examination results, as well as the surface of the ROMA index and the histopathological examination results. During the Assay Accuracy Verification phase of this study, a part of the qualified samples was randomly selected. The Sanger sequencing method was used as a comparison method to evaluate the detection accuracy of the test reagents for detecting the methylation of CDO1 and HOXA9 genes.

Official Title
-----------------
Exploration of Plasma CDO1 and HOXA9 DNA Methylation for Detecting Epithelial Ovarian Cancer: A Clinical Trial in China

Conditions
-----------------
Epithelial Ovarian Cancer, Circulating Tumor DNA, DNA Methylation, Non-invasive Diagnosis, CA125, Human Epididymis Protein 4, ROMA Index, Imaging Evaluation, Survival Prognosis

Intervention / Treatment
-----------------
* Diagnostic Test: Methylation assay


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ready for surgical treatment for pelvic mass or adnexal mass Age is greater than or equal to 18 years Not receiving any chemotherapy, physical therapy, or surgical treatment for ovarian lesions With ovarian pathology Willing to be tested and signed an informed consent form With available data of plasma CA125, Human epididymis protein 4 and effective imaging results The study will also enroll several patients with primary breast cancer, lung cancer, colon cancer, uterine cervical cancer and uterine carcinomas Exclusion Criteria: Not meeting all the including criteria A sample of patients withdrawing from the trial Samples that the investigator believes should be excluded from this trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Methylation assay|Methylation assay of CDO1 and HOXA9 genes in plasma circulating tumor DNA|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic sensitivity | Diagnostic sensitivity of methylation assay for detecting epithelial ovarian cancer | One month | 
| Diagnostic specificity | Diagnostic specificity of methylation assay for detecting epithelial ovarian cancer | One month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival after the last treatment for cancer | Two years |