A Novel Prognostic Factor TIPE2 in Bladder Cancer

Abstract

Objective: We sought to identify tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2/TNFAIP8L2) expression in bladder cancer and its relationship to clinicopathological findings and prognosis. Methods: Immunohistochemical (IHC) staining for TIPE2 was performed on 110 archived radical cystectomy specimens. Ten high-power fields were randomly selected from each specimen to observe and record the percentage of immunoreactive cells of TIPE2 in tumor cells (grade 0-4) and the corresponding immunostaining intensity (grade 0-3). The expression score of TIPE2 was obtained by multiplying the results of the above two scores, which ranged from 0 to 12 points. The cut-off point of the sum of the scores were defined as follows: 0-3 scores were defined as negative expression (-); >3 scores were classified as positive expression, < 7, low expression, ≥7, high expression. Results: In 110 cases, TIPE2 was stained in various degrees in bladder cancer tissues, and expressed in both nucleus and cytoplasm. 4.5% (5/110) showed negative expression, 40.9% (45/110) showed low expression, and 54.5% (60/110) showed high expression. TIPE2 expression was negatively correlated with lymph node metastasis (p = 0.004) and disease progression (p = 0.021). Survival curves were plotted to show that patients with high TIPE2 expression had a progression-free survival curve above those with negative/low TIPE2 expression (p = 0.027). In multivariate Cox proportional hazard regression analysis, TIPE2 was a protective factor for progression-free survival in bladder urothelial carcinoma (p = 0.031), pT stage (p = 0.016) was a risk factor for progression-free survival, and age was a risk factor for overall survival (p = 0.020). Conclusion: TIPE2 may be a new biomarker to predict the disease progression and prognosis of patients with urothelial carcinoma of the bladder.

Keywords: TIPE2; bladder cancer; cystectomy; epithelial-mesenchymal transition; urothelial carcinoma.