ZNF768 Expression Associates with High Proliferative Clinicopathological Features in Lung Adenocarcinoma

SIMPLE SUMMARY: Zinc-finger protein 768 (ZNF768) is a transcription factor that was recently shown to promote proliferation and repress senescence downstream of growth factor signaling in vitro. This protein was found to be overexpressed in a small cohort of lung adenocarcinoma (LUAD) compared to normal tissue, but its clinical value in this cancer remains unknown. The aim of this study was to determine whether ZNF768 associates with clinicopathological features in LUAD. We found that ZNF768 levels are often elevated in LUAD and that ZNF768 protein levels positively correlate with Ki-67 and other proliferative clinicopathological features in this cancer. Supporting a role for ZNF768 in promoting proliferation, ZNF768 depletion severely impairs proliferation in several lung cancer cell lines. Our study, that extends previous in vitro data, provides the first clinical observations supporting a possible role for ZNF768 in promoting cancer cell proliferation and tumor development in humans. ABSTRACT: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and a leading cause of cancer-related deaths worldwide. Despite important recent advances, the prognosis for LUAD patients is still unfavourable, with a 5 year-survival rate close to 15%. Improving the characterization of lung tumors is important to develop alternative options for the diagnosis and the treatment of this disease. Zinc-finger protein 768 (ZNF768) is a transcription factor that was recently shown to promote proliferation and repress senescence downstream of growth factor signaling. Although ZNF768 protein levels were found to be elevated in LUAD compared to normal lung tissue, it is currently unknown whether ZNF768 expression associates with clinicopathological features in LUAD. Here, using tissue microarrays of clinical LUAD surgical specimens collected from 364 patients, we observed that high levels of ZNF768 is a common characteristic of LUAD. We show that ZNF768 protein levels correlate with high proliferative features in LUAD, including the mitotic score and Ki-67 expression. Supporting a role for ZNF768 in promoting proliferation, we report that ZNF768 depletion severely impairs proliferation in several lung cancer cell lines in vitro. A marked decrease in the expression of key proliferative genes was observed in cancer cell lines depleted from ZNF768. Altogether, our findings support a role for ZNF768 in promoting proliferation of LUAD.