Abstract

Cancer remains one of the most common causes of mortality around the world and continues to evade standardization of diagnostic and therapeutic guidelines. As a multifaceted and heterogenous disease, development of standard screening options and monitoring cancer progression in patients is a challenge. In this study, we hypothesized that this challenge could be addressed by a biomarker that plays an essential and central role in oncogenesis across multiple cancer types. Previous studies from our labs and others have shown that Chaperonin Containing TCP-1 (CCT) is present in multiple cancers and plays an important role in oncogenesis as a protein folding complex of many oncogenes. Increased CCT levels in tissues correlate with increased cancer stage and severity, while inversely correlating with patient outcomes. For this project, we investigated the potential of the second subunit, CCT2, as a biomarker for adult cancers and pediatric cancers including breast cancer, lung cancer, and neuroblastoma. While most cancers have high levels of CCT, we used bioinformatics and histological studies to build a foundation for which cancers would benefit the most from our studies and were available for testing the feasibility of CCT2 as a biomarker. Since CCT2 has been studied in adult cancers previously, we first used breast cancer cells spiked in blood to adjust CCT2 as a biomarker for liquid biopsy. Once we determined a range of use for CCT2 in liquid biopsy, we tested it in lung cancer patients. Both showed increased recovery and promising circulating cells that were cytokeratin negative and CCT2 positive. To determine if CCT2 would also work in cancers with very different origins, we looked at pediatric cancers. We used neuroblastoma as our test model to determine if the CCT complex had a similar significance and role in pediatric cancers as in adult cancers. We completed overexpression and knockdown studies which showed results that were congruent with what CCT's role in adult cancer has been. We therefore tested sensitivity to CCT drug inhibition and sensitivity in liquid biopsy detection and determined that CCT is vital for tumorigenesis in neuroblastoma. These results show that CCT has the unique potential as a novel biomarker for cancer detection and that the second subunit could be used as a readout for the presence of the entire complex.

Notes

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Graduation Date

2022

Semester

Summer

Advisor

Khaled, Annette

Degree

Doctor of Philosophy (Ph.D.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Degree Program

Biomedical Sciences; MD/PhD Track

Identifier

CFE0009159; DP0026755

URL

https://purls.library.ucf.edu/go/DP0026755

Language

English

Release Date

8-15-2027

Length of Campus-only Access

5 years

Access Status

Doctoral Dissertation (Campus-only Access)

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Restricted to the UCF community until 8-15-2027; it will then be open access.

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