Background: Protein disulfide isomerase A3 (PDIA3), an endoplasmic reticulum protein, is expressed in bladder of BC patients. However, its role in BC has been elusive till now.
Objectives: This study was conducted to assess whether PDIA3 gene expression was associated with increased odds of BC, in particular muscle-invasive BC (MIBC).
Methods: Ninety three patients underwent cystoscopy and bladder tumors were biopsied and histologically assessed. Data collected including: patient demographics and clinical characteristics. Biochemical markers: hypoxia inducible factor 1-alpha (HIF-1 α), interleukin 6 (IL-6), advanced oxidation protein products (AOPP), Malondialdehyde (MDA), 8-hydroxy 2-deoxyguanosine (8-OHdG), and reduced glutathione (GSH) and molecular marker PDIA3 gene expression were measured.
Results: According to the tumor grade and stage, 36 patients were found to have MIBC, 27 patients have non MIBC (NMIBC) and 30 patients have no bladder lesions (control group). PDIA3 gene expression level had the largest contribution to a multivariable model for predicting BC, which achieved 89.0% predictive accuracy. The AUC for discriminating MIBC significantly increased from 0.644 to 0.938 when biochemical markers were replaced by molecular PDIA3 marker in the final model.
Conclusions: Using PDIA3 expression along with prior information of patient's age, bilharzial history with gross hematuria, can help clinicians predict BC, discriminate MIBC and decide consequently the most promising therapeutic management in Egyptian population.
Keywords: Bladder cancer; ER-stress; HIF-1α; IL-6; Oxidative stress; PDIA3.
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