Circulating small extracellular vesicles microRNAs plus CA-125 for treatment stratification in advanced ovarian cancer
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Published:2023-12-22
Issue:1
Volume:21
Page:
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ISSN:1479-5876
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Container-title:Journal of Translational Medicine
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language:en
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Short-container-title:J Transl Med
Author:
Zhou Xiaofang, Liu Mu, Sun Lijuan, Cao Yumei, Tan Shanmei, Luo Guangxia, Liu Tingting, Yao Ying, Xiao Wangli, Wan Ziqing, Tang JieORCID
Abstract
Abstract
Background
No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models.
Methods
RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets.
Results
Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p < 0.001; NRI = 0.122, IDI = 0.185, p < 0.01).
Conclusion
Overall, we established a reliable, non-invasive, and objective detection method composed of circulating tumor-derived sEVs 4-miRNA plus CA-125 to preoperatively anticipate the high-risk AOC patients of residual disease to optimize clinical therapy.
Funder
the General Project of Natural Science Foundation of Hunan Province Promotion Project of Health Suitability Program in Health Department of Hunan Province Science and Technology Innovation Program of Hunan Province Hunan Cancer Hospital Climbing Fund Capacity Building Project of Central Subsidy Medical and Health Institutions Key Specialty Construction Project in Hunan Province General Project in Health Department of Hunan Province
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
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