ISYNA1 is overexpressed in bladder carcinoma and regulates cell proliferation and apoptosis.

BACKGROUND: Bladder cancer (BCa) is one of the most common urological malignancies. While Inositol-3-phosphate synthase 1 (ISYNA1) expression and function were largely unknown in BCa. We aimed to study the expression and role of ISYNA1 in bladder cancer and investigate its potential mechanisms via ingenuity pathway analysis (IPA). METHODS: ISYNA1 expression was quantified by qRT-PCR in bladder cancer cell lines as well as normal urothelial cell line. Knocking down ISYNA1 gene in BCa T24 cells was achieved by shRNA lentivirus transfection. MTT and Celigo assay were used to assess cell proliferation. Flow cytometry was applied to test cell cycle and apoptosis. In addition, IPA was performed using PrimeView™ Human Gene Expression Array. Imunohistochemistry (IHC) was performed in BCa patient tissue microarray to verify the association between ISYNA1 expression and patients' clinicopathological features. RESULTS: ISYNA1 was significantly upregulated in BCa samples vs. para-tumor tissues. Higher expression were significantly associated with tumor T stage and lymph node metastasis of bladder cancer patients. Similarly, it was elevated in BCa cell lines (5637 and T24) compared with SVHUC cells. Knocking down ISYNA1 significantly decreased proliferation, induced apoptosis and cell cycle arrest in T24 cells. Furthermore, IPA indicated that ISYNA1 was an important regulatory factors and related networks were involved in multiple functional processes. CONCLUSION: Taken together, current study suggest ISYNA1 promotes proliferation and inhibit apoptosis in bladder cancer cells, and its expression correlated with BCa patients' clinicopathological features. Thus, ISYNA1 may serve as a potential biomarker and therapeutic target for BCa patients.

Comorbidity relationship to outcome of radical cystectomy in Chinese: a single institution study with the ACE-27 comorbidity index.

To determine the relationship between comorbidity and outcome after radical cystectomy in Chinese patients by using the Adult Comorbidity Evaluation (ACE)-27 index. Two-hundred-and-forty-six patients treated with radical cystectomy at the Second Xiangya Hospital of Central South University, Hunan Province, China between 2000 and 2010 were retrospectively analyzed. Medical records were reviewed for age, gender, delayed time of radical cystectomy, urinary diversion type, pelvic lymphadenectomy status, TNM stage, and pathological grade. Comorbidity information was assessed by the ACE-27 index. The outcome measurement was overall survival. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the association between comorbidity and outcome. The study population consisted of 215 (87.40%) males and 31 (12.60%) females with a mean age of 62±11 years. Median duration of follow-up was 47±31 months. A total of 151 (61.38%) patents died during follow-up. Of those, 118 (47.97%) had at least one comorbidity. According to the ACE-27 scores, 128 (52.03%) patients had no comorbidity, 79 (32.11%) had mild, 33 (13.41%) had moderate, and 6 (2.45%) had severe comorbidities. Multivariate analysis indicated that moderate (p=0.002) and severe (p<0.001) comorbidity was significantly associated with decreased overall survival. In addition, age ≥70 years (p=0.002), delayed time of radical cystectomy >12 weeks (p=0.044), pelvic lymphadenectomy status (p=0.014), and TNM stage >T3 (p<0.001) were determined to be independent risk factors of overall survival. Increasing severity of comorbidity statistically correlated with decreased overall survival after radical cystectomy.