Introduction: There is an urgent need to identify prognostic molecular markers in bladder cancer (BCa), which also act as potential therapeutic targets. Recent studies in some cancers have indicated that AHNKA2 would play an important role in regulating tumor progression pathways, such as phosphatidylinositol 3 kinase/protein kinase B and transforming growth factor-ß. However, there are no data regarding AHNAK2 in patients following radical cystectomy (RC) for BCa. The present study aimed to evaluate the expression levels of AHNAK2 and its’ prognostic role in the patients.
Methods: We retrospectively reviewed clinical data in 120 patients who underwent RC for BCa. The expression levels of AHNAK2 in the specimens of RC were immunohistochemically classified into low expression (LE) or high expression (HE) by a combined score of the intensity of staining with the percentages of positive tumor cells. Statistical analyses were performed to evaluate associations of the AHNAK2 expression patterns with the clinicopathological variables and the prognoses. To investigate the molecular mechanism, we additionally examined associations between AHNAK2 and S100A2, S100A4, S100A8, S100A9, and nestin. The Ethics Committee of Kitasato University School of Medicine and Hospital approved the study (B17-010, B18-149).
Results: Patients with HE had a significantly higher proportion of muscle-invasive BCa, lymph node metastasis and lymphovascular invasion (P = 0.047, P = 0.027 and P = 0.003, respectively) than those with LE. A Kaplan-Meier analysis showed that patients with HE had a significantly worse recurrence-free survival (RFS) and cancer-specific survival (CSS) than those with LE (P = 0.027 and P = 0.023, respectively). A multivariate analysis showed an independent risk factor for worse RFS and CSS as HE (hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.08-3.53, P = 0.026 and HR: 2.22, 95% CI: 1.14-4.31, P = 0.019, respectively). A subgroup analysis showed that patients with HE had a significantly higher proportion of S100A4, S100A8, S100A9, and nestin than those with LE (P < 0.05).
Conclusions: We found that high expression levels of AHNAK2 were associated with the aggressive pathological findings obtained by RC and were an independent factor for the worse survival in patients with RC. Associations between HE and S100 proteins, and nestin may highlight AHNAK2 as a novel therapeutic target of BCa. The present study showed that AHNAK2 acted as a novel prognostic biomarker in patients with RC for BCa.
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