Upregulation of BCL2 19 kD Protein-Interacting Protein 3 (BNIP3) is Predictive of Unfavorable Prognosis in Uveal Melanoma

• DOI: 10.12659/msm.907679
• Publication Date: 2018-07-08T11:14:12Z
• Authors: Zhongming Jiang; Fenghua Yu; Man Li
• Keywords: Adult; Male; Uveal Neoplasms; 0303 health sciences; Membrane Proteins; Middle Aged; Prognosis; Immunohistochemistry; Up-Regulation; 3. Good health; Survival Rate; 03 medical and health sciences; Clinical Research; Proto-Oncogene Proteins; Biomarkers, Tumor; Humans; Female; Melanoma; Aged

BACKGROUND BCL2 19 kD protein-interacting protein 3 (BNIP3) is a BH3-containing protein of the BCL-2 family; it can regulate cell death, autophagy, and cytoprotection. The upregulation of BNIP3 has been reported to relate to progression and poor prognosis in different cancer types. However, the clinical significance of BNIP3 in uveal melanoma (UM) is still unknown. MATERIAL AND METHODS In our study, 47 patients with UM were enrolled; the expression of BNIP3 was detected with immunohistochemistry. According to BNIP3 immunohistochemical scores, the patients were divided into BNIP3 high- and low-expression subgroups. The correlation between the expression of BNIP3 and clinicopathological factors was evaluated with Fisher's test; the associations with survival rates were analyzed with log-rank test. The independent prognostic factors were identified with the Cox-regression model. RESULTS BNIP3 was mainly localized in the cytoplasm, and high expression of BNIP3 accounted for 31.9% (15/47) of the patients in our study. High expression of BNIP3 was demonstrated to be significantly associated with more pigment (P=0.018) and deeper scleral invasion (P=0.013). High expression of BNIP3 was also correlated with lower overall survival rate (P=0.006). Multivariate analysis confirmed positive ciliary body involvement and lymphatic infiltration as independent prognostic factors. CONCLUSIONS High expression of BNIP3 was significantly associated with poor prognosis of patients with UM, indicating that BNIP3 detection could help stratify high-risk patients and identify new therapies targeting BNIP3 as a promising approach to treat UM.