Translational Significance of miRNAs to Optimize Diagnostics and Determination of Prognosis in Ovarian Cancer
Final Report Abstract
Ovarian cancer is characterized by high mortality rates due to late diagnosis urging the search for effective screening modalities. MicroRNAs (miRNAs), small non-coding RNA molecules that modify gene expression, have evolved as promising biomarkers for the early detection of ovarian cancer which can improve morbidity and mortality. For our studies we collected clinical data in over 1800 women with and without ovarian cancer and measured serum miRNA levels with an immunoassay in matching blood samples. Our approach of combining clinical metadata with a previously published miRNA neural network approaches (Elias et. al) showed an improvement in detecting ovarian cancers among adnexal masses compared to miRNA data only. In a cohort of over 1500 women without ovarian cancer we investigated which demographic and clinical factors may influence serum miRNA levels as this knowledge about possible confounding factors is crucial for refining clinical assays for cancer screening. Ovarian risk factors such as age, menopause, BRCA mutations as well as obesity, breast cancer in family history, prior bilateral oophorectomy, hypertension, and hypercholesterolemia significantly altered miRNA expression. Around 20% of ovarian cancers develop in women with germline BRCA mutations which most women are unaware of before their first cancer diagnosis. Known BRCA mutational carrier can access preventive measurements like risk reducing surgery or intensive screening. The combination of miRNA serum profiles plus clinical metadata can identify BRCA mutational carriers with a classification AUC score of 98% which exceeds AUC scores when only using miRNA sequencing data. This approach could help screening BRCA mutational carriers that might not be detected by the current protocols for BRCA testing. Our findings provide a framework for combining circulating biomarker data and clinical metadata in future studies.
Link to the final report
https://doi.org/10.4126/FRL01-006489564
Publications
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The impact of ovarian cancer risk factors on miRNA serum profiles in women without ovarian cancer. AACR-JCA joint conference: Breakthroughs in Cancer Research, Maui, December 2022
Laura Wollborn, James W. Webber, Sudhanshu Mishra, Marta Williams, Chad B. Sussman, Cameron E. Comrie, Daniel G. Packard, Stephanie Alimena & Kevin M. Elias
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MicroRNAs for characterizing and predicting BRCA mutations in women. BRCA Symposium, Montreal, May 2023
Laura Wollborn, James W. Webber, Sudhanshu Mishra, Chad B. Sussman, Cameron E. Comrie, Daniel G. Packard, Trinity Russell, Stephanie Alimena & Kevin M. Elias
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Serum miRNA expression in ovarian cancer patients is independent of histological subtype and FIGO stage. AACR Ovarian Cancer Conference, Boston, October 2023
Laura Wollborn, James W. Webber, Sudhanshu Mishra, Chad B. Sussman, Cameron E. Comrie, Daniel G. Packard, Allison Vitonis, Stephanie Alimena, Ryan Phan, Todd Pappas, Daniel W. Cramer, Dipanjan Chowdhury & Kevin M. Elias
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The impact of ovarian cancer risk factors on miRNA serum profiles in women without ovarian cancer. Dana-Farber/Harvard Cancer Center Breast and Gynecologic Cancer Symposium, Boston, April 2023
Laura Wollborn, James W. Webber, Sudhanshu Mishra, Marta Williams, Chad B. Sussman, Cameron E. Comrie, Daniel G. Packard, Stephanie Alimena & Kevin M. Elias
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Differences in Serum miRNA Profiles by Race, Ethnicity, and Socioeconomic Status: Implications for Developing an Equitable Ovarian Cancer Screening Test. Cancer Prevention Research, 17(4), 177-185.
Alimena, Stephanie; Stephenson, Briana Joy K.; Webber, James W.; Wollborn, Laura; Sussman, Chad B.; Packard, Daniel George; Williams, Marta; Comrie, Cameron Elizabeth; Wang, Joyce Y.; Markert, Tahireh; Spiegel, Julia; Rodriguez, Carmen B.; Lightfoot, Maya; Graye, Amia; O.'Connor, Sean & Elias, Kevin M.
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Effects of Clinical Covariates on Serum miRNA Expression among Women without Ovarian Cancer. Cancer Epidemiology, Biomarkers & Prevention, 34(3), 385-393.
Wollborn, Laura; Webber, James W.; Alimena, Stephanie; Mishra, Sudhanshu; Sussman, Chad B.; Comrie, Cameron E.; Packard, Daniel G.; Williams, Marta; Russell, Trinity; Fendler, Wojciech; Chowdhury, Dipanjan & Elias, Kevin M.
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Serum miRNA improves the accuracy of a multivariate index assay for triage of an adnexal mass. Gynecologic Oncology, 190, 124-130.
Webber, James W.; Wollborn, Laura; Mishra, Sudhanshu; Vitonis, Allison F.; Cramer, Daniel W.; Phan, Ryan T.; Pappas, Todd C.; Stawiski, Konrad; Fendler, Wojciech; Chowdhury, Dipanjan & Elias, Kevin M.
