Carolinas Research Day 2021

Biomedical Studies

07 Transmembrane and Tetratricopeptide Repeat Containing Isoforms as Novel Diagnostic Biomarkers for Prostate Cancer

Alexander S. Hernandez, OMSI, Dahir Hassan, OMSI, Zakaria Y. Abd Elmageed, MS, PhD

Edward Via College of Osteopathic Medicine-Louisiana

Introduction: Prostate cancer (PCa) is the most commonly diagnosed cancer in elderly men and the second leading cause of death for men in the United States. Although prostate specific antigen (PSA) is a routine marker for PCa, the sensitivity of PSA is compromised and may mislead treatment decisions upon tumor relapse. Therefore, there is an urgent need to develop a new reliable biomarker to stratify patients according to their clinical outcomes. We aimed to determine the clinical utility of novel transmembrane and tetratricopeptide repeat containing (TMTC) isoforms 2, 3 & 4 at different stages of PCa. Methods: The expression of TMTC3 and TMTC4 in PCa cells in addition to normal prostate epithelial cells was determined by Real-Time PCR and Western blot analyses. To determine the biological role of TMTC isoforms in PCa, ectopic expression of TMTC isoforms were performed in PCa cells. Functional

significance of TMTC3 and 4 was evaluated by cell proliferation, clonogenic and migration assays. In addition, immunohistochemical (IHC) studies was conducted using PCa tissue specimens. Results: Protein and IHC analyses showed that TMTC3 and 4 are differentially expressed in PCa cells versus their normal or BPH1 counterparts. Reconstitution of TMTC4 in low-expressed PCa cells increases the cell growth and cell migratory rates. IHC studies revealed that TMTC3 and 4 are overexpressed in tumors versus hyperplastic PCa tissues. Conclusion: TMTC 3 and 4 are overexpressed in PCa cells and tissues compared to normal controls and can be used as diagnostic markers. This study warrants further investigations to understand the underlying mechanisms of this protein in cancer progression.

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