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We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors. [ABSTRACT FROM AUTHOR]

Simple Summary: At present, the immunotherapy and immune microenvironment of bladder cancer have attracted more and more attention from clinicians and researchers. In this study, the high expression of SULF2 by RNA sequencing of tissues from 90 bladder cancer patients was associated with poor prognosis in patients. We further found that a high expression of SULF2 can promote the polarization of macrophages to M2. In mechanistic studies, we found that SULF2 can promote the secretion of IL-8 through Wnt/β-catenin. IL-8 promotes the transcription of CD163 and CD206 in the microenvironment, ultimately leading to the polarization of macrophages to M2 macrophages. This study elucidates the effect of SULF2 on the polarization of macrophages in the tumor microenvironment. Sulfatase 2 (SULF2) affects the occurrence and development of cancer by regulating HSPG-binding factors. However, the mechanism of SULF2 in bladder cancer (BCa) is unknown. To determine this, we analyzed the RNA sequencing of 90 patients with BCa. The results showed that the expression of SULF2 was closely related to the prognosis of BCa. Moreover, in vivo and in vitro experiments revealed that SULF2 promotes tumor proliferation and invasion. Furthermore, using a mouse orthotopic BCa model and flow cytometric analysis, we identified that SULF2 affects the polarization of macrophages. Mechanism studies clarified that SULF2 promoted the release of HSPG-binding factors, such as IL-8, in the microenvironment through β-catenin. Meanwhile, IL-8 activated the JAK2/STAT3 pathway of macrophages to promote the expression of CD163 and CD206, thereby regulating the polarization of macrophages to the M2-type. Conclusively, these results indicate that SULF2 plays an important role in regulating the microenvironment of BCa and promotes the polarization of macrophages to the M2-type by secreting IL-8, which further deepens the malignant progression of BCa. [ABSTRACT FROM AUTHOR]

Background: The effect of gender on the prognosis of bladder cancer (BCa) in different metastatic sites is insufficiently understood. We aimed to assess the impact and potential mechanisms of a combination of gender dimorphism and BCa metastasis sites on the risk of death. Methods: Independent predictors of overall survival and cancer-specific survival were analyzed after stratification by gender and metastasis sites from the Surveillance, Epidemiology, and End Results database. Furthermore, gender-differentially expressed genes (DEGs) and function-enriched annotations for patients with lymph node metastasis (LNM) were identified from The Cancer Genome Atlas (TCGA) database. A gender-associated signature was constructed in TCGA and validated in the IMvigor210 trial, and the magnetic resonance imaging-based radiomics signature was developed in our center to predict the gender-associated signature. Results: In patients with metastatic BCa, the most common site of metastasis is bone in men and lung in women. Moreover, stratified by sex, LNM had a better prognosis in men than visceral metastasis, which was not observed in female. Similarly, stratified by the metastasis site, the prognosis of men in patients with LNM is better than that of women, which was not observed in visceral metastasis patients. Enrichment of DEGs between sexes in patients with LNM may be related to metastasis and tumor immunity, especially the role of neutrophils. Moreover, the gender-associated signature is related to the clinicopathological characteristics of patients, and patients in the high-risk group had worse survival outcomes, and higher susceptibility to cisplatin, docetaxel, camptothecin, and paclitaxel. A nomogram combined with the signature and clinical staging showed significant predictive power in survival prediction. Furthermore, patients with high radiomics scores had a strong tendency for high-risk group. Conclusion: These results may improve the understanding of the differences in tumor biology between sexes and thus provide additional evidence for individualized treatment in BCa. [ABSTRACT FROM AUTHOR]

Objective: Imaging examination, tumor marker detection, bladder biopsy, and other methods are the common methods for the diagnosis of bladder cancer (BC). This study was aimed to assess the value of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) in the diagnosis of BC.Materials and Methods: Fifty-nine patients with BC were recruited in our hospital from September 2012 to December 2015, who had CEUS and magnetic resonance diffusion-weighted imaging (MRI + DWI). All patients underwent surgical treatment and definite pathological stage. The series and parallel combined diagnosis methods were applied to calculate the diagnostic sensitivity, specificity, and accuracy through using quantitative apparent diffusion coefficient (ADC) and receiver operating characteristic curve.Results: The accuracies of CEUS and MRI + DWI examination for T staging of BC were 74.6% and 76.3%, respectively. Compared with the single diagnostic methods, the two combined diagnosis accuracy was 91.5%, which was significantly improved in diagnosis accuracy (P < 0.05). The diagnostic accuracies of CEUS, MRI + DWI, and ADC for muscle invasion of BC were 81.4%, 83.1%, and 84.7%, respectively. The diagnostic accuracy of CEUS parallel combined with MRI + DWI (91.5%) was obviously enhanced, compared with that with the single diagnostic method.Conclusion: The accuracy of CEUS and MRI + DWI combined diagnosis was higher than that with the single diagnostic method. CEUS and MRI + DWI combined diagnosis was a feasible and effective method for the clinical diagnosis of BC. [ABSTRACT FROM AUTHOR]

As a diagnostic biomarker, the detection of circular RNA (circRNA) is vital for the early screening of bladder cancer. Usually, the low abundance of circRNA in clinic samples results in the necessarily complicated extraction before detection. In this work, a tetrahedron supported CRISPR/Cas13a cleavage has been explored for direct electrochemical detection of circRNA in urine from bladder cancer. CRISPR/Cas13a system has been reasonably designed to recognize the characteristic back-splice junction site of circRNA. The activated CRISPR/Cas13a by circRNA can cleave uracil bases composed of DNA tetrahedron immobilized on the surface of gold electrode, resulting in the breakage of DNA tetrahedron and the release of electrochemical active molecule methylene blue. By virtue of highly catalytic efficiency of CRISPR/Cas13a and rigid structure of tetrahedron, the developed electrochemical biosensor can directly detect circRNA in 25 μL urine sample with the lowest detection limit of 0.089 fM and linear detection range from 10 fM to 50 nM in less than 10 min, so as to avoid complicated extraction process and benefit for on-site detection. [ABSTRACT FROM AUTHOR]