Comparing Tribbles Homolog 3 (TRIB3) Protein Expression Levels with Clinicopathological Characteristics and Survival Among Neuroblastoma Patients

Abstract

Background: Tribbles Homolog 3 (TRIB3) is a member of the pseudokinase family of tribbles and acts as an adaptor protein to regulate different cellular processes. Upregulation of TRIB3 expression was shown either as a favorable or an adverse prognostic factor in various adult malignancies. However, TRIB3 expression has not been examined in pediatric cancers. Neuroblastoma is the most common malignant solid tumor of childhood, which affects mostly children under 5 years old. Risk stratification of patients defined by International Neuroblastoma Risk Group was used to determine prognosis and treatment of the disease. This study aimed to examine the relationship between TRIB3 protein expression levels and clinicopathological features and survival of patients. Methods: TRIB3 protein expression was analyzed using immunohistochemical staining on formalin-fixed paraffin-embedded tissue samples of neuroblastoma patients (n = 56). Survival analyses were performed with Kaplan-Meier method and log-rank tests. Association between TRIB3 expression and clinicopathological characteristics were analyzed with Spearman’s correlation. Results: Of the patients, 32.1% were in the low-risk group, 21.4% in the medium-risk group, and 46.4% in the high-risk group. Survival analysis was performed in the entire neuroblastoma patient group and sub-risk groups of neuroblastoma patients. In the entire patient group, there was no significant difference in overall survival ( P = .202) and event-free survival ( P = .172) between TRIB3-positive and -negative patients. However, when survival analyses were performed in each risk group, TRIB3 expression was significantly associated with higher overall survival ( P = .034) and event-free survival ( P = .032) in low-risk group neuroblastoma patients. Nevertheless, no association was found between TRIB3 expression and overall survival ( P = .799) and event-free survival ( P = .448) in high-risk neuroblastoma patients. Furthermore, a significant correlation was identified between 1p36 loss-of-heterozygosity and TRIB3 expression ( P = .030). However, TRIB3 expression did not correlate with other clinicopathological features. Conclusion: TRIB3 expression is a potential predictive biomarker for low-risk neuroblastoma patients.