Serum Mirna Expression in Ovarian Cancer Patients is Independent of Histological Subtype and FIGO Stage

Background: Serum miRNAs have been proposed as potential biomarkers for the early detection of ovarian cancer (OC). The heterogenous histological subtypes of ovarian cancer show different morphologic and genetic alterations influencing outcome and survival. We aimed to evaluate if serum miRNA levels differ with histological OC subtype and FIGO stage. Methods: We included women with histological confirmed OC from three study sets: 36 specimens from the Mass General Brigham Biobank collected between 2012 and 2019, 51 specimens from women in the pelvic mass study treated at the Brigham and Women’s Hospital (BWH) or Massachusetts General Hospital (MGH) between 1998 and 2009 and 93 specimens from Aspira Women’s Heath collected between 2007 and 2012. Data from 1790 women without OC from the Mass General Brigham Biobank collected between 2012 and 2019 were used as controls. Serum levels of a focused panel of 179 circulating miRNAs were measured by flow cytometry using the Abcam Fireplex® assay. Differences in miRNA serum profiles were analyzed according to histological subtypes and early (FIGO stage I/II) vs. late stages (FIGO stage III/IV) by univariate analysis, adjusting for multiple comparisons using Bonferroni correction. Results: The study population of OC patients showed a median age range of 50-59 years and 70.2% were postmenopausal, while women in the control group were younger (median age range of 40-49 years) and 48.3% were postmenopausal. Among the study subjects, most OC were of epithelial origin (174 OC (96.1%)) and consisted of the following histological subtypes: 87 (48.1%) serous, 29 (16.0%) endometrioid, 15 (8.3%) clear cell, 18 (9.9%) mucinous, 1 (0.6%) transitional cell, 24 (13.3%) other epithelial OC, and 7 (3.9%) non-epithelial OC. Most patients were diagnosed with advanced stage disease (59.1%) and showed a high-grade histology (59.7%). Univariate analysis showed significant changes in circulating miRNA profiles for epithelial OC compared to the control group with significant changes in 133/179 miRNAs (corrected p<0.05). No significant changes in miRNA expressions were detected comparing serous vs. non-serous epithelial OC and comparing any histological epithelial subtype (serous, endometrioid, clear cell or mucinous OC) to all other OCs in the study population. Further sub-group analyses comparing early vs. late-stage OCs among serous epithelial and non-serous epithelial OC did not reveal any significant differences in miRNA profiles, either. Conclusion: Ovarian cancers show a distinct miRNA profile, but different histological epithelial OC subtypes and tumor stages cannot be distinguished by miRNA expression levels. Detection of OC by miRNAs as potential biomarkers can be performed independent of histological subtype and tumor stage. Citation Format: 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. Serum miRNA expression in ovarian cancer patients is independent of histological subtype and FIGO stage [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B044.