Abstract C075: miRNAs linked to genome instability in ovarian high-grade serous carcinoma in patients with African ancestry
Authors: Muinde Jane M. , Carter Cody S , Khan Salma , Chang Hang , Maranga Innocent O. 
Published: September 2024

Abstract
Ovarian cancer is one of the most lethal gynecological malignancies worldwide, posing immense challenges in early detection, displaying grim prognoses, and having high rates of recurrence and mortality. This malignancy exhibits a range of ethnic diversity-mortality rates, each with distinct sub-categories characterized by variations in both molecular attributes and clinical behavior. The most prevalent and also most aggressive among the various ovarian cancer sub-types is high-grade serous ovarian carcinoma (HGSOC). This carcinoma is marked by genomic instability, resulting in the malfunction of tumor suppressor genes and oncogenes, caused by homologous recombination deficiency, copy number variations, chromosomal abnormalities, and epigenetic changes. The pursuit of understanding and targeting genomic instability has significantly guided approaches to screening, prognosis, and therapeutic strategies in ovarian cancer. Further insights from molecular investigations have unveiled the regulatory role of microRNAs (short non-coding RNAs) in modulating the expression of target tumor suppressors and oncogenes by interacting with messenger RNA (mRNA). Studies have shown that miRNAs are dysregulated in ovarian cancer, however, no data has shown significant relationships between these miRNAs to the patient demographics, including race/ethnicity. miRNAs can alter oncogenes, and tumor suppressor gene expression levels, serving as early biomarkers. We utilized the TCGA database from the University of Alabama at Birmingham (UALCAN) software to analyze the expressions of targeted genes and miRNAs. We determined various oncogenes and tumor suppressor genes with higher statistical significance on survival rates, race, cancer stages, tumor grades, and miRNAs linked to them. Additionally, genomic instability was assessed using aneuploidy score, fraction of genome altered, mutation counts, mutation burden, and prognosis (i.e., overall survival and progression-free survival), downloaded from cBioPortal, and the genomic instability parameters were calculated by Spearman correlation, and represented by a heatmap. Further, DNA and RNA from 22 HGSOC samples of paraffin-embedded tissues of ovarian cancer patients were collected for RT-qPCR assays for several miRNAs. Of the genes analyzed, BRCA1, BRAF, CCNE1, and miRNAs linked to these genes showed statistically significant data on survival rates. BRAF/CCNE1 is upregulated while BRCA 1 is downregulated in ovarian high-grade serous carcinoma. We also found quantitative differential expressions of some miRNAs analyzed in African Americans versus White Americans. Successful identification of early molecular markers in ovarian cancer will potentially allow for early detection and decreased mortality rates with HGSOC. Analysis of the appearance and abundance of miRNAs by qPCR assay in early-stage ovarian cancer can aid as an early diagnostic and prognostic tool. In a further study, we hope to verify our results by testing a larger cohort of samples from African Ancestry.
Citation Format: Jane M. Muinde, Cody S Carter, Salma Khan, Hang Chang, Innocent O. Maranga. miRNAs linked to genome instability in ovarian high-grade serous carcinoma in patients with African ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C075.