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.

A systematic review on diagnostic and prognostic biomarkers for bladder cancer

“…This finding could guide future research on bladder cancer tumor immunity. Jiang et al ., (2022) determined that TIPE2 was overexpressed in clinicopathological diagnosis and prognosis in bladder urothelial cancer, suggesting its employment as a potential protein biomarker for disease management. Jiang et al ., (2021) also identified OTX1 as a potential gene for the diagnosis and prognosis of bladder cancer, with carcinogenic effects through cell cycle-related pathways.…”

Structure, function, and mechanism of the TNFAIP8 (TIPE) family of proteins in cancer and inflammation

“…Interestingly, although TIPE1 and TIPE2 act as tumor suppressors in most cases, there is also some evidence that TIPE1 can act as an oncogenic factor to promote tumor cell growth and proliferation by inhibiting the acetylation of p53 in cervical cancer (Zhao et al, 2019). Moreover, TIPE2 shows low expression in bladder cancer, cervical cancer, and ovarian cancer, and the roles and related mechanisms in these cancers remain unclear (Zhang et al, 2011;Jiang et al, 2022;Zhang et al, 2022). Currently, the functions and mechanisms of TIPE3 have been reported to a lower extent.…”