Background: Bladder cancer (BCa) is a prevalent urologic malignancy that shows a poor prognosis. Abnormal metabolism and its key genes play a critical role in BCa progression. In this study, the role played by PhosphoGlycerol Dehydrogenase (PHGDH), an important molecule of serine metabolism, was investigated with regard to the regulation of ferroptosis in BCa.

Objective: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been shown to be an important prognostic marker in some tumor types. The aim of this study was to evaluate the prognostic impact of the preoperative HALP score, with the intent to develop a new prognostic index for patients with metastatic prostate cancer (mPCA) after cytoreductive radical prostatectomy (cRP).

Background: FGFR3 plays an important role in the development of bladder cancer (BCa). Hsa_circ_0068871 is a circRNA generated from several exons of FGFR3. However, the potential functional role of hsa_circ_0068871 in BCa remains largely unknown. Here we aim to evaluate the role of hsa_circ_0068871 in BCa. Methods: We selected miR-181a-5p as the potential target miRNA of hsa_circ_0068871. The expression levels of hsa_circ_0068871 and miR-181a-5p were examined in BCa tissues and paired adjacent normal tissues by quantitative real-time PCR. To characterize the function of hsa_circ_0068871, BCa cell lines were stably infected with lentivirus targeting hsa_circ_0068871, followed by examinations of cell proliferation, migration and apoptosis. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0068871 in BCa. Biotinylated RNA probe pull-down assay, fluorescence in situ hybridization and luciferase reporter assay were conducted to confirm the relationship between hsa_circ_0068871, miR-181a-5p and FGFR3. Results: Hsa_circ_0068871 is over-expressed in BCa tissues and cell lines, whereas miR-181a-5p expression is repressed. Depletion of has_circ_0068871 or upregulation of miR-181a-5p inhibited the proliferation and migration of BCa cells in vitro and in vivo. Mechanistically, hsa_circ_0068871 upregulated FGFR3 expression and activated STAT3 by targeting miR-181a-5p to promote BCa progression. Conclusions: Hsa_circ_0068871 regulates the miR-181a-5p/FGFR3 axis and activates STAT3 to promote BCa progression, and it may serve as a potential biomarker.

Background: The systemic immune-inflammation index (SII) has been used as a prognostic marker for several cancer types, but there is no in-depth study in bladder cancer. This study evaluated the potential utility of the SII as a prognostic factor in patients with bladder cancer after radical cystectomy. Methods: A retrospective analysis of 209 patients with bladder cancer who had undergone radical cystectomy and were randomized into primary (N=139) and validation (N=70) cohorts was conducted. The overall survival (OS) was calculated using the Kaplan-Meier survival curves. The prognostic value of the SII in primary and validation cohorts were analyzed by using the Cox regression model. A SII-based nomogram for bladder cancer was produced in R software. Results: A high SII (>507) was associated with poor prognosis in bladder cancer patients. Univariate and multivariate analyses revealed that the SII was an independent predictor for OS. The SII emerged as an independent prognostic factor that provided more accurate prognostic prediction than neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein/albumin ratio (CAR), in the primary and validation cohorts. The nomogram had better accuracy and discrimination than tumor, lymph node, metastasis (TNM) classification. The concordance index values of nomogram were 0.82 for the primary cohort and 0.784 for the validation cohort. Conclusions: The SII can serve as an independent predictor of OS in patients who have undergone radical cystectomy for bladder cancer, and was found to be a better predictor of prognosis than NLR, PLR, and CAR. The nomogram is a reliable model for predicting postoperative OS of patients after radical cystectomy.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in tryptophan metabolism and plays an important role in tumor cell immunosuppression and angiogenesis. The molecular mechanisms of IDO1 and epithelial-mesenchymal transition (EMT) have not been elucidated or studied in bladder cancer. Therefore, the aims of this study were to detect IDO1 expression in bladder cancer tissues and then to investigate the role of IDO1 in bladder cancer cell EMT and malignant phenotypes as well as the underlying molecular mechanisms. By immunohistochemistry, Western blot, and quantitative reverse transcription-polymerase chain reaction experiments, IDO1 was found to be overexpressed in bladder cancer tissues and cell lines compared to the noncancerous ones. In addition, knockdown of IDO1 expression was shown to inhibit bladder cancer cell growth, migration, invasion, and EMT. Furthermore, we demonstrated that IDO1 may promote EMT by activation of the interleukin 6/signal transducer and activator of transcription 3/programmed cell death ligand 1 signaling pathway. Collectively, these data suggest that IDO1 may play an important role in bladder cancer and may be a novel therapeutic target for patients with bladder cancer.

The present study investigated the possible tumor-suppressing function of microRNA (miR)-612 and the underlying molecular mechanism of its action in bladder cancer in vitro and in vivo. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was carried out to quantify the expression levels of miR‑612 in bladder cancer tissues and cell lines. The data demonstrated that the level of miR‑612 expression was significantly reduced in bladder cancer tissues and cell lines, as compared with that in non‑cancerous tissues and cells. Reduced miR‑612 expression was associated with advanced tumor, lymph node and metastasis stages, and with distant metastasis of bladder cancer. A functional study revealed that transfection of cells with an miR‑612 mimic suppressed bladder cancer cell growth, colony formation, migration, invasion and epithelial-mesenchymal transition. Bioinformatics analysis identified that miR‑612 targeted the expression of malic enzyme 1 (ME1), and this was confirmed by western blot and luciferase reporter assay results. Furthermore, the ME1 expression levels were inversely associated with miR‑612 expression in bladder cancer tissue specimens. In addition, knockdown of ME1 expression using ME1 siRNA mimicked the effect of ectopic miR‑612 overexpression in bladder cancer cells in terms of tumor cell growth, migration and invasion. By contrast, ME1 overexpression weakened the inhibitory effect of the miR‑612 mimic in bladder cancer cells. In conclusion, the present study demonstrated that miR‑612 may function as a tumor suppressor in bladder cancer by targeting ME1 expression.