Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Comparison of the survival outcomes between primary and secondary muscle-invasive bladder cancer: a propensity score-matched study / 中华医学杂志(英文版)

BACKGROUND@#Studies have classified muscle-invasive bladder cancer (MIBC) into primary (initially muscle-invasive, PMIBC) and secondary subtypes (initially non-muscle-invasive but progresses, SMIBC), for which controversial survival outcomes were demonstrated. This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.@*METHODS@#Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included. Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics. Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes. Propensity score matching (PSM) was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.@*RESULTS@#A total of 405 MIBC patients were enrolled, including 286 PMIBC and 119 SMIBC, with a mean follow-up of 27.54 and 53.30 months, respectively. The SMIBC group had a higher proportion of older patients (17.65% [21/119] vs. 9.09% [26/286]), chronic disease (32.77% [39/119] vs . 22.38% [64/286]), and neoadjuvant chemotherapy (19.33% [23/119] vs . 8.04% [23/286]). Before matching, SMIBC had a lower risk of overall mortality (OM) (hazard ratios [HR] 0.60, 95% confidence interval [CI] 0.41-0.85, P  = 0.005) and cancer-specific mortality (CSM) (HR 0.64, 95% CI 0.44-0.94, P  = 0.022) after the initial diagnosis. However, higher risks of OM (HR 1.47, 95% CI 1.02-2.10, P  = 0.038) and CSM (HR 1.58, 95% CI 1.09-2.29, P  = 0.016) were observed for SMIBC once it became muscle-invasive. After PSM, the baseline characteristics of 146 patients (73 for each group) were well matched, and SMIBC was confirmed to have an increased CSM risk (HR 1.83, 95% CI 1.09-3.06, P  = 0.021) than PMIBC after muscle invasion.@*CONCLUSIONS@#Compared with PMIBC, SMIBC had worse survival outcomes once it became muscle-invasive. Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.

Research advances of urinary cell-free DNA in the detection and therapy of bladder cancer / 中华泌尿外科杂志

Bladder cancer is a common malignancy in the genitourinary system and the current therapeutic approaches are unsatisfactory. Urinary cell-free DNA (ucf DNA) has the ability to give comprehensive and crucial information on cancer as it carries genetic messages from cells shedding directly into urine as well as transporting from circulation. The ucf DNA of patients with bladder cancer carries disease information, suggesting that ucf DNA may have the ability to detect, monitor, and prognosticate patients with bladder cancer. The ucf DNA analysis bridges the gap between current techniques and enhances diagnostic and detection capabilities, and has a very promising future in term of translation into clinical practice. This article reviewed the progress of clinical applications of ucf DNA in bladder cancer.

Efficacy of the biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy in the detection of prostate cancer / 中华泌尿外科杂志

Objective:To investigate the efficacy of the biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy on prostate cancer (PCa) detection in biopsy-na?ve patients.Methods:The clinical data of 121 biopsy-na?ve patients who underwent transperineal prostate biopsy in West China Hospital of Sichuan University from July 2018 to January 2020 were retrospectively analyzed. The average age was (64.7±9.1) years old. Pre-biopsy prostate-specific antigen (PSA) was (12.4±7.5)ng/ml, f/t PSA was 0.13±0.05. Prostate volume was (43.1±26.1) ml and PASD was (0.35±0.27) ng/ml 2. The prostate-imaging and data system (PI-RADS) score of MRI before biopsy was reported to be 3 for 29 patients (24.0%), 4 for 54 patients (44.6%) and 5 for 38 patients (31.8%). All 121 patients underwent 12-core systematic biopsy combined with a 3-core or 5-core MRI-targeted biopsy, of which 61 patients underwent 3-core targeted biopsy and 60 underwent 5-core targeted biopsy. There was no significant difference in the pre-biopsy clinical data between the two groups ( P>0.05). A 6-core systematic biopsy was redefined as the results of 6 cores among the 12-core systematic biopsy. We compared the detection rates among the single 12-core systematic biopsy, 6-core systematic biopsy, MRI-targeted biopsy (3-core or 5-core), and different systematic biopsy combing with targeted biopsy for any PCa and clinically significant PCa, and we also analyzed the cumulative cancer detection rates for MRI-targeted biopsy of different cores. Results:Of the 121 patients in this study, the biopsy results were negative for 43 patients (35.5%) and positive for 78 (64.5%). The detection rate of clinically significant PCa was 55.4% (67/121). The detection rate of the 6-core systematic biopsy combined with MRI-targeted biopsy was 62.0% (75/121) for PCa and 55.4% (67/121) for clinically significant PCa, which was of no difference compared with that for the 12-core systematic biopsy combined with MRI-targeted biopsy ( P>0.05), but the 6-core systematic biopsy combined with MRI-targeted biopsy avoided the overdiagnosis of 3 patients with Gleason score 3+ 3. The detection rate of PCa for MRI-targeted biopsy was 57.9% (70/121), including 42.1% (51/121) for the first core, 55.4% (67/121) for the first two cores, and 57.9% (70/121) for the first three cores. Compared with the single-core targeted biopsy for suspicious lesions, the first 2-core targeted biopsy ( OR=1.7, 95% CI 1.0-2.8) and 3-core targeted biopsy ( OR=1.9, 95% CI 1.1-3.1) can significantly increase the detection rate of PCa, while the fourth or fifth core of targeted biopsy can not increase the detection rate additionally (60%, 36/60). Conclusion:For patients with suspected PCa, the prostate biopsy strategy combing 6-core systematic and 3-core MRI-targeted biopsy performs no inferior than the current 12-core systematic biopsy combined with MRI-targeted biopsy.