Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades

Objective: The role of ureteroscopy in the diagnosis of upper tract urothelial carcinoma is yet to be fully determined. We aimed to provide an up to date evaluation of its role and the emerging technologies in the field.Methods: A literature search of the last two decades (from 24th May, 2001 to 24th May, 2021) was carried out identifying 147 papers for potential inclusion within this narrative review.Results: Diagnostic ureteroscopy is undeniably useful in its ability to visualise and biopsy indeterminate lesions, and to risk stratify malignant lesions that may be suitable for kidney sparing surgery. However, an increased risk of intravesical recurrence following nephroureterectomy when a prior diagnostic ureteroscopy has been performed, inadequate sampling at biopsy, complications from the procedure, and difficult ureteric access are all potential drawbacks. Furthermore, whilst generally an accurate diagnostic procedure, it risks missing carcinoma in-situ lesions. Despite this, evidence shows that routine use of ureteroscopy changes the management of patients in a large proportion of cases, preventing unnecessary surgery or facilitating kidney sparing surgery. The overall rate of complications is low, and improved biopsy techniques and the use of tissue biomarkers for improved staging and grading are encouraging. The risks of delays to definitive management and post-ureteroscopy intravesical recurrence do not seem to affect survival, and trials are in progress to determine whether intravesical therapy can mitigate the latter. Further promising techniques are being investigated to improve shortcomings, particularly in relation to improved diagnosis of carcinoma in situ and preoperative staging.Conclusion: Ureteroscopy has a role in the diagnosis of upper tract malignancy, though whether it should be used routinely is yet to be determined.

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

Expression of Multidrug-associated Protein, P-glycoprotein, P53 and Bcl-2 Proteins in Bladder Cancer and Clinical Implication

The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P gp, P53 and Bcl 2 was 52.5 %, 57.5 %, 47.5 % and 62.5 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in the grade Ⅰ, Ⅱ and Ⅲ of tumors was 46.3 %, 38.5 %, 38.5 %, 23.1 %; 52.9 %, 39.8 %, 47.1 %, 76.4 %; 60.0 %, 80.0 %, 60.0 %, 90.0 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in 24 primary tumor specimens was 37.5 %, 41.7 %, 33.3 %, 45.8 % and that in 16 cases in recurrent specimens receiving chemotherapy 75.0 %, 81.3 %, 68.8 %, 87.5 % respectively. It was suggested the positive rate of MRP, P gp, P53 and Bcl 2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased ( P <0.05). The expression of MRP, P gp, P53 and Bcl 2 proteins might be the important factors for chemotherapy failure.

Clinical significance of elevation of serum CA125 level in patients with metastatic bladder carcinoma

Objective： To explore the clinical significance of the examination of serum CA125 level of patients with metastatic bladder carcinoma. Methods： Electrochemiluminescence technique was used to examine the serum CA125 concentration of 58 cases with metastatic bladder cancer. 30 cases of superficial bladder cancer and 8 cases of other urological diseases were collected as the control group. Results： Serum CA125 level in 39 （67.2%） out of 58 cases ranged from 36.7 U/mL to 1485.6 U/mL （mean 496.3 U/mL）, being higher than normal （〈 35 U/mL）. Serum CA125 level of metastatic bladder cancer patients was 324.5 U/mL, significantly higher than that in control group （P 〈 0.001）. Serum CA125 level of 10 patients after transurethral resection operation was significantly lower than that before operation （P 〈 0.05）. Serum CA125 level of 16 patients who refused further treatment significantly increased from 450.4 U/mL, to 505.8 U/mL （P = 0.041） 3 months after discharge from the hospital. Serum CA125 level of 17 patients significantly decreased from 475.8 U/L to 237.9 U/mL （P 〈 0.001 ） after bilateral iliac-artedal embolism treatment. Conclusion： CA125 may be a valuable marker for the judgment of advanced metastatic bladder cancer.

Superselective embolisation of bilateral superior vesical arteries for management of intractable hematuria in context of metastatic bladder cancer

Hematuria due to locally advanced or metastatic bladder cancer is a common condition and is often a management problem.Percutaneous embolisation is a mini-invasive option to handle this situation.We report a case of a patient with a metastatic bladder cancer and who presented with an abundant hematuria and severe anemia.After failure of endoscopic resections and“flush”of radiotherapy haemostatic and refusal of cystectomy by the patient,he was treated by superselective embolisation of bilateral superior bladder arteries with excellent immediate results.The technique is safe and effective in the short term.The longterm effectiveness requires further investigation.

Clinicopathologic Observation of 6 Cases with Neuroendocrine Carcinoma of the Urinary Bladder

OBJECTIVE To discuss the pathologic characteristics and theprognosis of neuroendocrine carcinoma of the bladder(NECB)in order to assist in making a precise diagnosis and to effectivelytreat the disease.METHODS Clinicopathologic features of the 6 cases with NECBwere analyzed retrospectively.The personal data of the patientsand the pathologic and immunohistochemical characteristics ofthe tumor were investigated.The follow-up of these patients wasconducted over a time period ranging from 3 months to 9 years.RESULTS Transurethral resection of the bladder tumorwas performed in all 6 patients.Based on the results of thepathologic examination,4 of the cases were diagnosed as smallcell neuroendocrine carcinoma and the other 2 were diagnosedas atypical carcinoid tumor.On immunohistochemical stainingall tumors expressed neuroendocrine markers includingneuronspecific enolase(CD56),synaptophysin(Syn)andchromogranin(CgA).In patients receiving partial cystectomyfollowed by postoperative chemotherapy,relapse was found in 4of the 6 cases on follow up.CONCLUSION NECB is a rare entity and a tumor with highmalignant potential and characteristic pathologic features.Hematuria is the cardinal symptom of NECB.Metastasis mayoccur at an early stage and the prognosis of the disease is poor.Final diagnosis of NECB depends on histopathologic examinationand immunohistochemical assays.Surgical excision combinedwith radiotherapy and chemotherapy is considered an effectivetreatment.

Successful treatment of solitary bladder plasmacytoma:A case report

BACKGROUND Plasmacytoma is a rare neoplastic disorder that arises from B-lymphocytes.Solitary bladder plasmacytoma,a type of solitary extramedullary plasmacytoma,is even rarer.Treatments for solitary extramedullary plasmacytoma include surgery,chemotherapy,and radiation.However,there are no clinical trials or guidelines specifying which treatment might represent the gold standard.CASE SUMMARY We herein report a case of a 51-year-old woman with solitary bladder plasmacytoma(SBP).There remains no consensus regarding the optimal treatment for SBP.However,we successfully treated her with transurethral resection of bladder tumor followed by postoperative radiotherapy(50 Gy/25 F).The patient remained free of tumor recurrence at a 7-mo follow-up.CONCLUSION Radiation is the potential main treatment for SBP.However,surgery is also necessary.

Expression of connexin43 and its correlation with the expressions of Bcl-2 and Bax proteins in transitional cell carcinoma of the bladder

Objective: To study the expression of connexin43 (Cx43) gene and its correlation with the apoptosis related genes Bcl-2 and Bax in transitional cell carcinoma of the bladder (BTCC), and to investigate the role of Cx43 in the BTCC. Methods: Reverse transcription polymerase chain reaction was used to detect the expression of Cx43 mRNA and immunocytochemistry technique was used to detect the expressions of Bcl-2 and Bax proteins in 60 cases of BTCC tissues, and compared with that of 15 cases of pericancerous tissues and 15 cases of normal bladder tissues. Results: The positive expression rate of Cx43 mRNA in 60 cases of BTCC tissues was 43.33% which was significantly lower than that in pericancerous tissues (73.33%) and normal tissues (100%) (χ2 = 17.58, P < 0.01). The expression of Cx43 had significant negative correlation with the pathological degree and lymph node metastasis of BTCC (χ2 = 9.33 and 9.74, respectively, P < 0.01). However, no correlation was found between the expression and patient sex, age, clinical staging and diameter and growth pattern of BTCC (P > 0.05). Expression of Cx43 negatively correlated with Bcl-2 protein (r = -0.63, P < 0.01) and positively correlated with Bax protein (r = 0.52, P < 0.01). Conclusion: The down-regulated expression of Cx43 gene was closely associated with the development, invasion and metastasis of BTCC. It could be used as a prognostic indicator for BTCC. Cx43 gene may have antagonistic effects with Bcl-2 gene and synergic with Bax gene in the initiation and progression of BTCC.

Immediate cystectomy or conservative management for T_1 G_3 bladder cancer: A meta-analysis of general survival rate

Objective： The aim of this study was to compare the therapeutic effects of bladder preserving approach transurethral resection （TURBT） with additional intravesicel instillation versus immediate cystectomy in patients with newly diagnosed stage T1G3 bladder cancer. Methods： Clinical data of patients with newly diagnosed T1G3 bladder cancer underwent immediate cystectomy （Group A） or TURBT with additional intravesical instillation （Group B） was collected from online databases. Meta-analysis that recommended by Cochrane Collaboration was done for the data obtained. Publication bias was examined using a funnel plot. Results： Four trails, including 434 patients, were eligible for this study. The general mortality rate of group A （74/149 = 49.7%） and group B （102/285 = 35.8%） was calculated and compared in RevMan 4.2, which showed the difference on general mortality rate between the two groups was not statistical significant, with the pooled RR = 1.23 （95% CI 1.10-1.70, P 〉 0.05）. Conclusion： Compared with TURBT, immediate cystectomy may not reduce the general mortality rate to improve the forward survival rate.

Establishment of orthotopic transplantation model of human bladder cancer and detection by MRI

Objective: To establish an orthotopic bladder cancer model bearing human bladder cancer for experimental research, and monitor tumor progression by magnetic resonance imaging (MRI). Methods: The mucosa was mechanically damaged transurethrally under direct vision, and then human bladder cancer cell line T24 was inoculated into the bladders of BALB/c nude mice to establish orthotopic bladder cancer model. To find a suitable concentration of Gd-DTPA for this re- search. MRI was performed weekly to assess tumor growth, using Gd-DTPA as contrast agent. The pathologic morphology of the bladders and other specimens were observed with HE stain. Results: All the 25 mice developed bladder cancer after inoculation. The best concentration of Gd-DTPA was 1.408 mg/mL. On MRI, no change in the bladders was observed on day 7 after inoculation, filling defect in the bladders, accordant to actual tumor size, was detected on days 14, 21 and 28. Pathologic examination showed that tumor grew in the mucosa or superficial muscle of bladder on day 7, confined in muscle layer on days 14–28, and invaded serosa on day 35. Conclusion: Transurethrally damaged bladder mucosa under direct vision and instilled bladder cancer cell T24, we successfully established an orthotopic bladder cancer model. Tumor growth simulated the progression of human bladder cancer approximately. MRI was a reliable way for dynamic detection of murine orthotopic bladder tumor.

Expression of Glutathione S-transferase π in Human Bladder Cancer

The purpose of this study was to investigate the expression of glutathione stransferase (GST) and its clinical significance in human bladder cancer. GST immunoreactivity was assessed respectively in 49 bladder cancers and 30 normal bladder mucosas by avidin biotin peroxidase complex (ABC) techniques. The corelationship of GST expression and clinical and biological feature of bladder cancer was studied. Positive GST was observed in 44 cases of bladder cancer mucosa (89.8%) and in 18 cases of normal bladder mucosa (60%). In 42 cases of stage G\-\{12\} and 7 cases of stage G\-3 cancer patients the positive GST expression rate was 80.9%(34/42) and 100%(7/7) respectively. In 14 cases of recurrent bladder cancer the total positive expression rate was 92.9% (13/14), meanwhile in 19 cases of stage T23 the positive nuclear staining was seen in 10. Higher rate of GST expression was found in bladder cancer than in normal bladder mucosa, which was implied that the resistance to chemotheraputic drugs in bladde r cancer might be related to the expression of GST. GST expression was correlated with tumor grade. Furthermore, increased intranuclear GST expression might be associated with bladder cancer progression.

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Costimulatory Molecule B7-H1 on the Immune Escape of Bladder Cancer and Its Clinical Significance

B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con- structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence （P〈0.05）. The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.

Correlative Expression of Glutathion S-Transferase-π and Multidrug Resistance Associated Protein in Bladder Transitional Cell Carcinoma

In order to elucidate the mechanisms of multidrug resistance (MDR) in bladder cancer, the expression of glutathione S-transferase-π (GST-π) and multidrug resistance associated protein (MRP) in tissue samples resected from 44 patients and 6 normal bladder mucosa as control was de- tected by using immunohistochemical method, and the results were analyzed by computer-assisted im- age analyzing system (IAS) to achieve semi-quantitative data. In addition, correlation between the expression of both factors was studied. The results showed that the positive expression rate of GST- π and MRP in bladder cancer was 72. 7 % (32/44) and 68. 2 % (30/44) respectively, significantly higher than those in normal bladder mucosa, being 16. 7% and 33. 3% respectively. The rate of GST-πpositive staining was increased correspondingly with tumor grade and stage elevated, being higher in recurrent tumors treated by chemotherapy, but not significantly (P>0. 05). There was no significant differences between the expression of MRP and tumors' behaviors and clinical characters. However, the results demonstrated that the correlation between the expression of both resistant fac- tors was very evident (r=0. 695, P<0. 0025). It was suggested that the activation of GST-π and MRP might occur during malignant transformation of normal mucosa, but tumors' differentiation and progression could not be the unique factors that influenced both overexpression. Chemotherapy might be another important reason. The correlation of both indicated that there was a common mech- anism regulating their expression probably, which made them play a pivotal role in chemotherapy drug resistance of bladder cancers.

Plasmacytoid Transitional Cell Carcinoma of Bladder： A Clinico-pathological Study and Review of Literatures

Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

Detection of Smac expression in bladder cancer and its clinical significance

Objective： To detect the expression of second mitochondria-derived activator of caspase （Smac） in bladder cancer and discuss its clinical significance. Methods： Smac was detected in 15 specimens of normal bladder epithelium and 72 specimens of bladder cancer by reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry at the level of gene and protein, respectively. Results： The differences of both Smac protein and mRNA expressions between normal mucous membrane of bladder and grade i bladder cancer had no statistical significance （ P 〉 0.05 ）. The expressions of Smac protein and its mRNA in bladder cancer decreased gradually with the advance of bladder cancer （ P 〈 0.01 and P 〈 0.05, respectively）. In invasive bladder cancer, the expressions of Smac protein and its mRNA were higher than those in superficial bladder cancer （ P 〈 0.01）. Conclusions： Normal bladder epithelium has high expression of Smac while bladder cancer has low expression of Smac. The expression of Smac is closely related to the grade and stage of bladder cancer. Detection of Smac expression helps to judge the grade and stage of bladder cancer and Smac gene might become a valid target for gene therapy of bladder cancer.

ALTERATION OF G1-CYCLINS (D1 AND E) IN TRANSITIONAL CELL CARCINOMA OF HUMAN URINARY BLADDER WITH INFECTION OF HPV-18

Objective: This study was designed to investigate differential pattern of G1-cyclins (D1 and E) in transitional cell carcinoma (TCC) of human urinary bladder with or without human papillomavirus-18 (HPV-18) infection. Methods: Immunohistochemistry method was used in the detection of the expression of G1-cyclins in 57 cases of TCC (7 normal bladders as control), and HPV-18 DNA was found in 29 cases by polymerases chain reaction (PCR). Results: Cyclin D1 expression was found in 41 of 57 (71.93%) TCCs and it was reverse associated with HPV (x 2=8.21, P<0.05). And cyclin D1 expression was found in 16 of 29 (55.17%) in HPV-18 infection group and 25 of 28 (89.29%) in non-HPV infection group. Cyclin E expression was detected in 36 of 57 (63.16%) and the association between the cyclin E expression and HPV infection was not found (x2=0.52, P>0.05). Cyclin E expression was found in 17 of 29 (56.82%) in HPV-18 infection group and 19 of 28 (67.86%) in non-HPV infection group. There was obvious difference in the cyclin D1 and cyclin E expression between the TCC and normal tissue (x 2=7.46, P<0.05; x 2=7.45, P<0.05, respectively). Conclusion: These data demonstrated that HPV infection altered the control of G1 cell cycle. And changes of G1 cell cycle regulatory proteins, either by interaction of cellular protein with viral oncoproteins or by changes in the cellular proteins themselves, may be critical for carcinogenesis of TCC of urinary bladder.

CLINICAL SIGNIFICANCE OF TELOMERASE ACTIVITY AND PERIPHERAL VENOUS BLOOD CK-20 EXPRESSION IN BLADDER TRANSITIONAL CELL CARCINOMA

Objective: The relationship between peripheral blood CK-20 mRNA expression and tissue telomerase activity in bladder transitional cell carcinoma (TCCB) was investigated to evaluate the feasibility of their combined detection in early-stage diagnosis and prognosis estimation of TCCB. Methods: the blood CK-20 was detected by semi-nested RT-PCR and telomerase activity in tumor tissue was examined with silver-stained TRAP reaction. Results: the blood CK-20 expression and tissue telomerase activity in TCCB were 41% and 93% respectively. No statistical significance was detected among pathological grading and clinical staging (P>0.05). Positive correlation was shown between CK-20 expression and telomerase activity with the pathologic grade or clinical stage. Conclusion: combined use of blood CK-20 and tissue telomerase activity detections might be of great importance for clinical diagnosis, treatment and prognosis evaluation.

SMALL CELL CARCINOMA OF THE URINARY BLADDER: THREE CASES REPORT

To study the clinical features of patients with primary small cell carcinoma (SCC) of the bladder and to improve the diagnosis and treatment. Methods: Clinical data of 3 cases with primary SCC of the bladder were discussed and the pathology, diagnosis, treatment and prognosis were reviewed. Results: 3 cases of primary SCC of the bladder were presented. Of them the diagnosis was confirmed by pathological examination after operation (2 cases) and biopsy (1 case). One case with stage T4M1 died after three months?chemotherapy. One case with stage T2M0 underwent partial cystectomy and was treated with chemotherapy and one year later died of miocardial infarction. Another case with stage T4M0 underwent radical cystectomy and postoperative irradiation therapy. The patient was alive and had no recurrence of symptoms during two years follow-up. Conclusion: Primary SCC of the urinary bladder is highly malignant. Radical cystectomy combined with radiotherapy appears to be the efficient treatment. Chemotherapy seems to be of no significant effect.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

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 microbarrier 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 integrinβ8(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.