Abstract
BackgroundThe identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer.Methodology/Principal FindingsWe used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels.We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients.Conclusions/SignificanceWe implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers.
Highlights
Ovarian cancer is the leading cause of gynecological cancer deaths and the fifth leading cause of all cancer-related deaths in women
We sought to circumvent some of the limitations associated with the biomarker development process [29]
One problem with biomarkers identified by high throughput technologies is their lack of sufficient specificity [29]
Summary
Ovarian cancer is the leading cause of gynecological cancer deaths and the fifth leading cause of all cancer-related deaths in women. Since early stage disease is often asymptomatic, and there is no effective screening strategy, most patients (62%) present with advanced-stage (III and IV) disease, in which the cancer has spread throughout the peritoneal cavity or other organs [1]. It is anticipated that effective methods for detection of asymptomatic ovarian cancer before invasion and metastasis has occurred would substantially reduce the mortality rate for this disease. Sensitive detection methods could be applied to monitoring disease recurrence after tumor resection with or without adjuvant chemotherapy. The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
