IDENTIFYING EARLY STEPS IN THE DEVELOPMENT OF HBV ASSOCIATED HCC

The hepatitis B virus (HBV), chronically infecting ~360 million people worldwide, accounts for over half of the cases of hepatocellular carcinoma (HCC) and contributes to over 650,000 deaths per year making HCC is the fifth most common and second most deadly form of cancer.1-3 Many genes deregulated by the hepatitis B x-antigen (HBx), the oncogenic protein encoded by HBV, are known drivers of HCC.4,5 The timing of these alterations in the initiation and progression of disease, however, are poorly understood and the treatment options for HCC are extremely limited. Here, RNA-Seq expression data originally from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project were used to compare truly healthy liver tissues, a base-line level often excluded from cancer studies, to both non-tumor and tumor tissues of patients with HBV associated HCC. This illuminated inflammation and immune response process as dysregulated prior to tumor formation followed by disruption of cell cycle and cell survival processes once tumors have arisen. Connecting these processes are UBD, BCL6, METTL24, CHRNA4, and NFKBIZ which putatively serve as crucial early drivers in the progression from HBV infection to the development of HCC and affect the serum level of downstream targets which could serve as biomarkers for earlier disease detection. Differential methylation analysis was also carried out on samples directly from TCGA and the Gene Expression Omnibus (GEO) to determine if the differentially expressed genes were potentially deregulated due to reversible epigenetic alterations. Enriched pathways for differential methylation in non-tumor samples included the immune system and the cell cycle but none of the genes of interest from differential expression analysis were differentially methylated until stage 1 indicating that methylation is involved in the progression of disease and not initiation.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2020

Author dc:creator

• Ropars, Lisa Marie

Advisor dc:contributor.advisor

• Feitelson, Mark

Committee members dc:contributor.committeemember

• Kulathinal, Rob J.
• Pond, Sergei
• Jelinek, Jaroslav

• Biology
• Cancer
• Hepatitis
• Liver

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/20.500.12613/3494

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/3494