Jaynish S Shah1, Gregory B Gard2, Jean Yang3, Jayne Maidens2, Susan Valmadre4, Patsy S Soon5, Deborah J Marsh6. 1. Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia. 2. Department of Obstetrics and Gynaecology, Royal North Shore Hospital, St. Leonards, Australia. 3. School of Mathematics and Statistics, University of Sydney, Camperdown, New South Wales, Australia. 4. Mater Private and Royal North Shore Hospitals, Sydney, NSW, Australia. 5. South Western Sydney Clinical School, University of New South Wales, Bankstown, New South Wales, Australia; Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool Hospital, New South Wales, Australia. 6. Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia. Electronic address: deborah.marsh@sydney.edu.au.
Abstract
OBJECTIVES: The most widely used approach for the clinical management of women with high-grade serous ovarian cancer (HGSOC) is surgery, followed by platinum and taxane based chemotherapy. The degree of macroscopic disease remaining at the conclusion of surgery is a key prognostic factor determining progression free and overall survival. We sought to develop a non-invasive test to assist surgeons to determine the likelihood of achieving complete surgical resection. This knowledge could be used to plan surgical approaches for optimal clinical management. METHODS: We profiled 170 serum microRNAs (miRNAs) using the Serum/Plasma Focus miRNA PCR panel containing locked nucleic acid (LNA) primers (Exiqon) in women with HGSOC (N=56) and age-matched healthy volunteers (N=30). Additionally, we measured serum CA-125 levels in the same samples. The HGSOC cohort was further classified based on the degree of macroscopic disease at the conclusion of surgery. Stepwise logistic regression was used to identify predictive markers. RESULTS: We identified a combination of miR-375 and CA-125 as the strongest discriminator of healthy versus HGSOC serum, with an area under the curve (AUC) of 0.956. The inclusion of miR-210 increased the AUC to 0.984; however, miR-210 was affected by hemolysis. The combination of miR-34a-5p and CA-125 was the strongest predictor of completeness of surgical resection with an AUC of 0.818. CONCLUSION: A molecular test incorporating circulating miRNA to predict completeness of surgical resection for women with HGSOC has the potential to contribute to planning for optimal patient management, ultimately improving patient outcome.
OBJECTIVES: The most widely used approach for the clinical management of women with high-grade serous ovarian cancer (HGSOC) is surgery, followed by platinum and taxane based chemotherapy. The degree of macroscopic disease remaining at the conclusion of surgery is a key prognostic factor determining progression free and overall survival. We sought to develop a non-invasive test to assist surgeons to determine the likelihood of achieving complete surgical resection. This knowledge could be used to plan surgical approaches for optimal clinical management. METHODS: We profiled 170 serum microRNAs (miRNAs) using the Serum/Plasma Focus miRNA PCR panel containing locked nucleic acid (LNA) primers (Exiqon) in women with HGSOC (N=56) and age-matched healthy volunteers (N=30). Additionally, we measured serum CA-125 levels in the same samples. The HGSOC cohort was further classified based on the degree of macroscopic disease at the conclusion of surgery. Stepwise logistic regression was used to identify predictive markers. RESULTS: We identified a combination of miR-375 and CA-125 as the strongest discriminator of healthy versus HGSOC serum, with an area under the curve (AUC) of 0.956. The inclusion of miR-210 increased the AUC to 0.984; however, miR-210 was affected by hemolysis. The combination of miR-34a-5p and CA-125 was the strongest predictor of completeness of surgical resection with an AUC of 0.818. CONCLUSION: A molecular test incorporating circulating miRNA to predict completeness of surgical resection for women with HGSOC has the potential to contribute to planning for optimal patient management, ultimately improving patient outcome.
Authors: Jie Liu; Li Li; Ning Luo; Qi Liu; Li Liu; Dandan Chen; Zhongping Cheng; Xiaowei Xi Journal: Exp Ther Med Date: 2020-12-21 Impact factor: 2.447