Bcl-2 and Noxa are potential prognostic indicators for patients with gastroenteropancreatic neuroendocrine neoplasms.

ABSTRACT

PURPOSE: Bcl-2 family proteins are of great significance in the pathogenesis and development of tumors. In this study, the correlations between the expression of Bcl-2 family proteins and clinicopathological features and prognosis of neuroendocrine neoplasms (NENs) were further investigated. METHODS: 105 Patients diagnosed with gastroenteropancreatic NENs (GEP-NENs) with the paraffin specimen of the tumor available were retrospectively included. Immunohistochemistry (IHC) was performed to detect the expression of Bcl-2 family proteins in paraffin-embedded samples. Student's t-test and Chi-square test were applied to compare the difference of quantitative and categorical variables, respectively. Survival analysis was conducted according to Kaplan-Meier method. Univariate and multivariate cox regression analysis were used to identify the independent prognostic factors. RESULTS: The IHC score of Bcl-2 was significantly higher in neuroendocrine carcinoma (NEC) patients (65.6%), while a higher IHC score of Noxa was more common in neuroendocrine tumor (NET) patients (49.3%). Survival analysis indicated that patients with higher Bcl-2 expression and lower Noxa expression had worse 5-year survival (39.3% vs. 75.6%, p < 0.001; 40.6% vs. 84.9%, p < 0.001). Multivariate cox analysis indicated that high Bcl-2 expression was an independent factor associated with inferior DFS (hazard ratio [HR] 2.092; 95% confidence interval [CI] 1.106-3.955; p = 0.023) and OS (HR 2.784; 95% CI 1.326-5.846; p = 0.007), while higher Noxa expression was associated with superior DFS (HR0.398; 95% CI 0.175-0.907; p = 0.028) and OS (HR 0.274; 95% CI 0.110-0.686; p = 0.006). CONCLUSIONS: Higher expression of Bcl-2 and lower expression of Noxa were associated with unfavorable prognosis of GEP-NENs patients.