Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma

Mohammed Tanjimur Rahman, Kentaro Nakayama, Munmun Rahman, Naomi Nakayama, Masako Ishikawa, Atsuko Katagiri, Kouji Iida, Satoru Nakayama, Yoshiro Otsuki, Ie-Ming Shih, Kohji Miyazaki
Cancer 2012 June 1, 118 (11): 2846-57

BACKGROUND: The goal of this study was to examine the clinical significance of ZNF217 amplification and assess whether ZNF217 could be a potential therapeutic target in ovarian clear cell carcinoma (OCCC).

METHODS: ZNF217 expression and amplification in OCCC was assessed by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected via a retrospective chart review. ZNF217 gene knockdown using silencing RNA (siRNA) was used to assess ZNF217 functions in OCCC cell lines.

RESULTS: Gene amplification was identified in 12 of 60 (20.0%) OCCCs. ZNF217 copy number correlated significantly with ZNF217 protein expression (r = 0.341; P<.01). ZNF217 amplification correlated significantly with shorter progression-free (P = .0042) and overall (P = .0199) survival. There were nonsignificant trends between high ZNF217 protein expression and poor progression-free (P = .2594) and overall (P = .2199) survival. Multivariate analysis revealed ZNF217 gene amplification to be an independent prognostic factor for progression-free and overall survival after standard platinum agent-based chemotherapy (P = .0339 and P = .031, respectively). Profound growth inhibition and apoptosis were observed in ZNF217 siRNA-treated cancer cells with gene amplification compared with cancer cells with ZNF217 moderate expression without ZNF217 gene amplification or with low ZNF217 expression.

CONCLUSION: These findings indicate that ZNF217 overexpression is critical to growth and survival of OCCCs with ZNF217 gene amplification. Furthermore, they suggest that ZNF217 siRNA-induced phenotypes depend on amplification status of OCCCs. Therefore, ZNF217-targeted therapy may benefit OCCC patients with ZNF217 amplification.

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