MicroRNA Signatures in Serous Ovarian Cancer: A Comparison of Prognostic Marker Targets in African Americans and Caucasians

TL;DR

This study identifies microRNA signatures linked to racial disparities in ovarian cancer outcomes between African American and Caucasian patients.

Contribution

The paper discovers distinct miRNA–mRNA regulatory signatures, particularly the miR-192-5p–ITGB1/TIMP3 axis, as potential biomarkers for racial disparities in ovarian cancer.

Findings

ITGB1, TIMP3, and BRAF are significant prognostic genes in serous ovarian cancer.

miR-192-5p shows strong statistical significance in TCGA data and correlates with poorer survival.

African American patients show higher expression of ITGB1 and TIMP3 compared to Caucasians.

Abstract

Ovarian cancer (OC) is the second most common gynecologic cancer in the United States, causing more deaths than any other cancer of the female reproductive system. Mortality rates for ovarian cancer of recent African origin, compared to those of either Asian or American ancestry, have increased over the years. Identifying microRNA signatures associated with racial disparities can be an effective prognostic tool in the clinic. In this study, we identified significant genetic prognostic markers and microRNA signatures linked to them. We used both Formalin-fixed paraffin-embedded and fresh ovarian tumor tissue samples from African American and Caucasian patients with serous ovarian cancer. Total RNA extraction was performed on the tumor tissue samples, and quantitative PCR was used to determine the differential expression of various microRNAs linked to the identified prognostic markers. Determining microRNA signatures in ovarian cancer will provide information about their potential clinical relevance for future diagnosis, prognosis, and therapeutics.

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer.

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