Enriched miRNA-mRNA pair pathways in hepatocellular carcinoma for patients of different racial backgrounds

Amber Alley (Mentor: Dr. Habtom Ressom, Department of Oncology, Georgetown University)

August 28, 2018, 2:00pm, Room 1300, Harris Building

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is found mostly in patients who have chronic liver diseases, such as cirrhosis. While there has been substantial research of HCC as a whole, there is a large gap in race-based HCC research. The goal of this project is to determine enriched miRNA-mRNA pathways in HCC patients of different racial backgrounds in order to identify how the disease affects different races and what role the relationship between miRNA-mRNA plays in those effects.  The tissue samples (divided into Asian American, European American, and African American groups) include HCC infected tissue along with adjacent cirrhosis and adjacent normal tissue. We compared the HCC tissue to the adjacent normal tissue and to the adjacent cirrhosis tissue within each race and for all races combined (total HCC vs adjacent normal tissue and total HCC vs adjacent cirrhosis tissue). miRNA and mRNA expression levels in these samples were determined by next generation sequencing. After the RNA-seq and miRNA-seq data were aligned and preprocessed, we were able to use the miRNA and mRNA expression data together to find enriched pathways for miRNA-mRNA pairs in Ingenuity Pathway Analysis (IPA). IPA has the capacity to determine these enriched paired pathways by using a curated literature database. Filtering was applied to each data set before using pathway analysis (p-value 0.05, FDR 0.05) (Of note, the cirrhosis data, due to it being the smallest sample pool, produce few results after filtering). The data produced was then compared to other various pathway enrichment tools. While many pathways expressed were the same across the different races, we found that there were unique pathways being expressed in the different racial groups that show a connection to HCC in varying degrees. As the sample size for this study is fairly small, this study’s determined pathways will hopefully aid in guiding future race-based HCC studies that are able to utilize larger sample sizes.