Discipline: Biological Sciences
Subcategory: Cancer Research
Aliyah Patterson - University of the District of Columbia, Washington D.C
Co-Author(s): Prachi Mishra, Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, MD; Brandy Huderson, University for the District of Columbia, Washington D.C; Shiv Srivastava, Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, MD, and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD; Albert Dobi,Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, MD, and John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD
Background: Predicting the clinical course of prostate cancer (CaP) is challenging due to the wide spectrum of the biological features. Immunohistochemical studies identified Tenascin C (TNC) as one of the promising markers associated with poor prognosis (Ni et al., BBRC 2017). TNC has been shown to play a role in promoting metastatic tumor environment in breast cancer models (Oskarsson et al., Nat. Medicine 2012). TNC is a hexameric, extracellular matrix glycoprotein that is expressed in several cancer tissues such as the breast, lung, colon, and the gastrointestinal tract causing proliferation, migration, invasion, angiogenesis, and metastasis. However, the role of TNC in prostate cancer is not completely understood. This study aims the characterization of TNC in prostate cancer progression.
Methods: Publically available prostate cancer databases were examined (cBioPortal) that showed either amplifications or mutations in TNC. We queried the the status of TNC along with known driver genes of prostate tumorigenesis, including ERG, MYC and AR, in the aggressive neuroendocrine prostate cancer (NEPC) tumor whole genome sequencing datasets (N=77).
Results: We found that 74% of the patients characterized with NEPCs showed alterations predominantly amplifications and also, mutations, deep deletion or multiple rearrangements. At CaP genomic levels TNC (30%) was significantly co-amplified with ERG (27%), AR (56%) and MYC (53%). We further investigated the level of mRNA and protein expression of TNC in various prostate cancer cell lines such as VCaP, LNCaP, PC3 and DU145. TNC protein expression was detected in all examined prostate cancer cell lines.
Conclusion: Genomic alterations (primarily amplification) of TNC is associated with major oncogenic drivers of CaP, such as ERG, AR and MYC in NEPC genomic datasets. Further studies are warranted to address the mechanistic link between TNC and major CaP oncogenic pathways in the context of NEPC phenotype.
Funder Acknowledgement(s): This research was funded by a grant from USUHS, W81XWH-14-2-0142
Faculty Advisor: Dr. Brandy Huderson, firstname.lastname@example.org
Role: 75% of the data being presented was collected by me and the other 25% was collected prior to me joining the project.