The outcome of bladder cancer after radical cystectomy is heterogeneous. We aim to evaluate the prognostic value of HALP (hemoglobin, albumin, lymphocyte and platelet) and explore novel prognostic indexes for patients with bladder cancer after radical cystectomy. In this retrospective study, 516 patients with bladder cancer after radical cystectomy were included. The median follow-up was 37 months (2 to 99 mo). Risk factors of decreased overall survival were older age, high TNM stage, high American Society of Anesthesiologists (ASA) grade and low HALP score. The predictive accuracy was better with HALP-based nomogram than TNM stage (C- index 0.76 ± 0.039 vs. 0.708 ± 0.041). By combining ASA grade and HALP, we created a novel index—HALPA score and found it an independent risk factor for decreased survival (HALPA score = 1, HR 1.624, 95% CI 1.139–2.314, P = 0.007; HALPA score = 2, HR 3.471, 95% CI: 1.861–6.472, P < 0.001).The present study identified the prognostic value of HALP and provided a novel index HALPA score for bladder cancer after radical cystectomy.

5-Hydroxymethylcytosine (5hmC) is converted from 5-methylcytosine (5mC) by a group of enzymes termed ten-eleven translocation (TET) family dioxygenases. The loss of 5hmC has been identified as a hallmark of most types of cancer and is related to tumorigenesis and progression. However, the role of 5hmC in bladder cancer is seldom investigated. Vitamin C was recently reported to induce the generation of 5hmC by acting as a cofactor for TET dioxygenases. In this study, we explored the role of 5hmC in bladder cancer and the therapeutic efficacy of vitamin C in increasing the 5hmC pattern. 5hmC was decreased in bladder cancer samples and was related to patient overall survival. Genome-wide mapping of 5hmC in tumor tissues and vitamin C-treated bladder cancer cells revealed that 5hmC loss was enriched in cancer-related genes and that vitamin C treatment increased 5hmC levels correspondingly. Vitamin C treatment shifted the transcriptome and inhibited the malignant phenotypes associated with bladder cancer cells in both in vitro cell lines and in vivo xenografts. This study provided mechanistic insights regarding the 5hmC loss in bladder cancer and a rationale for exploring the therapeutic use of vitamin C as a potential epigenetic treatment for bladder cancer.

Metastasis is the primary cause of tumor death in renal cell carcinoma (RCC). Improved diagnostic markers of metastasis are critically needed for RCC. MicoRNAs are demonstrated to be stable and significant biomarkers for several malignancies. In this study, we aimed to explore the metastasis related microRNAs and its mechanism in RCC. The relationship between microRNAs expression and prognosis and metastasis of RCC patients were explored by data mining through expression profiles from The Cancer Genome Atlas (TCGA). A total of 80 RCC tissues and adjacent normal kidney tissues were obtained from Department of Urology, Peking University First Hospital. Expression of microRNA-200b (miR-200b) in RCC tissues and cell lines were determined by bioinformatic data mining and quantitative real-time PCR (qRT-PCR). The effects of miR-200b on cell proliferation, migration and invasion were determined by cell counting kit-8 and colony formation assay, wound healing assay and Boyden chamber assay. Mouse cell-derived xenograft and patient-derived xenograft model were also performed to evaluate the effects of miR-200b on tumor growth and metastasis in vivo. The molecular mechanism of miR-200b function was investigated using bioinformatic target predication and high-throughput cDNA sequencing (RNA-seq) and validated by luciferase reporter assay, qRT-PCR, Western blot and immunostaining in vitro and in vivo. Our findings indicates that miR-200b is frequently downregulated and have potential utility as a biomarker of metastasis and prognosis in RCC. Interestingly, ectopic expression of miR-200b in the Caki-1 and OSRC-2 cell lines suppresses cell migration and invasion in vitro as well as tumor metastases in vivo. However, miR-200b has no effect on cell proliferation in vitro and tumor growth in vivo. In addition, bioinformatics target predication and RNA-seq results reveals that Laminin subunit alpha 4 (LAMA4) is one target of miR-200b and significantly inhibited by miR-200b in vitro and in vivo. These results demonstrate a previously undescribed role of miR-200b as a suppressor of tumor metastasis in RCC by directly destabilizing LAMA4 mRNA.

BACKGROUND: Current noninvasive assays for urothelial carcinoma (UC) lack clinical sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) biomarkers, the development of urinary cfDNA biomarkers may improve the diagnostic sensitivity.METHODS: We assessed copy number alterations (CNAs) by shallow genome-wide sequencing of urinary cfDNA in 95 cancer-free individuals and 65 patients with UC, 58 with kidney cancer, and 45 with prostate cancer. We used a support vector machine to develop a diagnostic classifier based on CNA profiles to detect UC (UCdetector). The model was further validated in an independent cohort (52 patients). Genome sequencing data of tumor specimens from 90 upper tract urothelial cancers (UTUCs) and CNA data for 410 urothelial carcinomas of bladder (UCBs) from The Cancer Genome Atlas were used to validate the classifier. Genome sequencing data for urine sediment from 32 patients with UC were compared with cfDNA. To monitor the treatment efficacy, we collected cfDNA from 7 posttreatment patients.RESULTS: Urinary cfDNA was a more sensitive alternative to urinary sediment. The UCdetector could detect UC at a median clinical sensitivity of 86.5% and specificity of 94.7%. UCdetector performed well in an independent validation data set. Notably, the CNA features selected by UCdetector were specific markers for both UTUC and UCB. Moreover, CNA changes in cfDNA were consistent with the treatment effects. Meanwhile, the same strategy could localize genitourinary cancers to tissue of origin in 70.1% of patients.CONCLUSIONS: Our findings underscore the potential utility of urinary cfDNA CNA profiles as a basis for noninvasive UC detection and surveillance.

Long non-coding RNA HNF1A-AS1 promotes proliferation and suppresses apoptosis of bladder cancer cells through upregulating Bcl-2 Long non-coding RNA HNF1A-AS1 promotes proliferation and suppresses apoptosis of bladder cancer cells through up-regulating Bcl-2