Clinicopathological Characteristics of TZAP Expression in Colorectal Cancers

Onco Targets Ther. 2020 Dec 17:13:12933-12942. doi: 10.2147/OTT.S274394. eCollection 2020.

Abstract

Purpose: The zinc finger protein, ZBTB48, is a telomere-associated protein. It was renamed as telomeric zinc finger-associated protein (TZAP) binding to elongated telomeres. However, its expression level was not measured in cancers.

Patients and methods: We analyzed TZAP mRNA levels in 60 colorectal cancers (CRC) and its correlation with telomere length and TERT was studied.

Results: TZAP mRNA in CRC was higher statistically than that in paired non-cancerous tissues (p = 0.033). Higher TZAP was found in carcinoembryonic antigen (CEA)-positive CRCs (>5 ng/mL) (p = 0.012). Shorter telomere was found in CRCs with high TZAP expression than that with low TZAP expression (p = 0.010). According to quantitative correlation analysis, TZAP has a correlation with age (r = -0.349, p = 0.007), TERT (r = 0.279, p = 0.041) and telomere length (r = -0.305, p = 0.021). TZAP expression did not harbor prognostic value in CRC. Inhibition of TZAP expression by siRNA suppresses cell growth in HT29 cells; however, it resulted in increased cell viability in HCT116 cells. TZAP inhibition induces a decrease in mRNA levels of TERT in both HT29 and HCT116 cells. TCGA data analysis showed higher expression of TZAP showed poorer overall survival in colon cancer (p = 0.001); however, it did not have a significance in rectal cancer (p = 0.951).

Conclusion: We suggested that TZAP may be a possible biomarker for CRC.

Keywords: TZAP; ZBTB48; colorectal cancer; telomere.

Grants and funding

This research was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Korean Government (MSIP), grant number 2014R1A5A2010008.