Roles of ferroptosis in urologic malignancies

Ferroptosis, an iron-dependent form of non-apoptotic cell death, is believed to strongly contribute to the pathogenesis of multiple cancers. Recently, the positive association between ferroptosis and urologic malignancies has drawn considerable attention, while a comprehensive review focused on this issue is absent. Based on this review, ferroptosis has been implicated in the development and therapeutic responses of prostate cancer, kidney cancer, and bladder cancer. Mechanistically, a large number of biomolecules and tumor-associated signaling pathways, including DECR1, PANX2, HSPB1, ACOT8, SUV39H1, NCOA4, PI3K-AKT-mTOR signaling, VHL/HIF-2α pathway, and Hippo/TAZ signaling pathway, have been reported to regulate ferroptosis in urologic cancers. Ferroptosis inducers, such as erastin, ART, CPNPs, and quinazolinyl-arylurea derivatives, exert potential therapeutic effects per se and/or enhance the anticancer response of other anticancer drugs in urologic oncology. A better understanding of ferroptosis may provide a promising way to treat therapy-resistant urologic cancers.

MicroRNA as a Biomarker for Diagnostic, Prognostic, and Therapeutic Purpose in Urinary Tract Cancer

The incidence of urologic cancers, including kidney, upper tract urothelial, and bladder malignancies, is increasing globally, with a high percentage of cases showing metastasis upon diagnosis and low five-year survival rates. MicroRNA (miRNA), a small non-coding RNA, was found to regulate the expression of oncogenes and tumor suppressor genes in several tumors, including cancers of the urinary system. In the current review, we comprehensively discuss the recently reported up-or down-regulated miRNAs as well as their possible targets and regulated pathways involved in the development, progression, and metastasis of urinary tract cancers. These miRNAs represent potential therapeutic targets and diagnostic/prognostic biomarkers that may help in efficient and early diagnosis in addition to better treatment outcomes.

The Impact of Metformin Use with Survival Outcomes in Urologic Cancers: A Systematic Review and Meta-Analysis

Background. Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer). Methods. We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs). Results. Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence ( HR = 0.74 ; 95% CI: 0.61-0.90; P = 0.007 ; I 2 = 56 % ), CSS ( HR = 0.74 ; 95% CI: 0.61-0.91; P = 0.002 ; I 2 = 79 % ), and OS ( HR = 0.76 ; 95% CI: 0.65-0.90; P < 0.001 ; I 2 = 86 % ). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression ( HR = 0.80 ; 95% CI: 0.65-0.98; P = 0.14 ; I 2 = 46 % ). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: HR = 0.76 ; 95% CI: 0.59-0.98; P = 0.88 ; I 2 = 0 % ). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years ( HR = 0.43 ; 95% CI: 0.28-0.67; P = 0.61 ; I 2 = 0 % ).

Comprehensive Characterization of Common and Cancer-Specific Differently Expressed lncRNAs in Urologic Cancers

Urologic cancers, comprising prostate carcinoma (PCa), renal cell carcinoma (RCC), and bladder carcinoma (BCa), were the commonly occurred carcinoma amid males. Long noncoding RNAs (lncRNAs) with the length of more than 200 nt functioned importantly in physiological and pathological advancement. Nevertheless, further investigation regarding lncRNA expression feature and function in urologic cancers should be essential. This study is aimed at uncovering the roles of the differently expressed lncRNAs in urologic cancers. The data of gene expression levels was downloaded from lncRNAtor datasets. The lncRNA expression pattern existing in different urologic cancers was assessed by hierarchical clustering analysis. Gene Ontology (GO) analysis and KEGG pathway analysis were separately applied to evaluate the biological function and process and the biological pathways involving differently expressed lncRNAs. Our results indicated that 18 lncRNA expressions were increased, and 16 lncRNA expressions were reduced in urologic cancers after comparison with that in normal tissues. Moreover, our results demonstrated 61, 422, 137, and 281 lncRNAs were specifically dysregulated in bladder cancer (BLCA), kidney renal clear cell cancer (KIRC), kidney renal papillary cell cancer (KIRP), and prostate adenocarcinoma (PRAD), respectively. Bioinformatics analysis showed that differently expressed lncRNAs displayed crucially in urologic cancers. The prognostic value of common and cancer-specific differently expressed lncRNAs, such as PVT1, in cancer outcomes, was emphasized here. Our research has deeply unearthed the mechanism of differently expressed lncRNAs in urologic cancers development.