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Family with sequence similarity 84, member B (FAM84B) is a significant copy number amplification gene in the 8q24.21 locus identified by our previous WGS study in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance and potential mechanisms have been elusive. Here, we performed the association analyses between FAM84B Amp  and clinicopathological features using 507 ESCC samples. The results indicated that, compared with the FAM84B non-Amp  patients ,  the FAM84B Amp  patients showed a more aggressive and a worse prognosis. A significant correlation was discovered between the expression level of FAM84B and FAM84B Amp  in the ESCC cohort. Furthermore, we found that the forced expression change of FAM84B can influence ESCC cell proliferation and cell-cycle status, which is probably mediated by NPM1. A direct interaction between FAM84B and the C-terminal (189–294aa) of NPM1 was identified, which increased the NPM1 nuclear expression. Over-expression of NPM1 could inhibit the CDKN2A protein expression, which might affect the ESCC cell cycle. Our results indicate FAM84B CNA may be a potential diagnostic and therapeutic biomarker in ESCC, meanwhile, reveal a novel mechanism of FAM84B that promotes tumorigenesis via interacting with NPM1 and suppressing CDKN2A.

Elevated FAM84B promotes cell proliferation via interacting with NPM1 in esophageal squamous cell carcinoma