Accurate prognostic prediction for patients with clear cell renal cell carcinoma using a ferroptosis-related long non-coding RNA risk model.

INTRODUCTION: Ferroptosis is a recently discovered type of programmed cell death that plays a crucial role in tumor occurrence and progression. However, no prognostic model has been established yet for clear cell renal cell carcinoma (ccRCC) using ferroptosis-related long non-coding RNAs (lncRNAs). METHODS: In the present study, lncRNA expression profiles, sex, age, TMN stage, and other clinical data of ccRCC samples were extracted from The Cancer Genome Atlas database. In addition, ferroptosis-related lncRNAs were identified using co-expression analysis, and the risk model was established using Cox regression and least absolute shrinkage and selection operator regression analyses. Log-rank test and Kaplan-Meier analysis were performed to evaluate the predictive accuracy of the risk model for the overall survival (OS) of patients with ccRCC. Moreover, the functional enrichment of ferroptosis-related lncRNAs was performed and visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. RESULTS: Eight prognostic ferroptosis-related lncRNAs were identified, such as LINC01615, AC026401.3, LINC00944, AL590094.1, DLGAP1-AS2, AC016773.1, AC147651.1, and AP000439.2, making up the ferroptosis-related lncRNA risk model. The risk model effectively divided patients with ccRCC into high- and low-risk groups, and their survival time was calculated. The high-risk group showed significantly shorter OS compared to the low-risk group. The nomogram to predict the survival rate of the patients revealed that the risk score was the most critical factor affecting OS in patients with ccRCC. The ferroptosis-related lncRNA risk model was an independent predictor of prognostic risk assessment in patients with ccRCC. CONCLUSION: The ferroptosis-related lncRNAs risk model and genomic clinicopathological nomogram have the potential to accurately predict the prognosis of patients with ccRCC and could serve as potential therapeutic targets in the future.

Molecular Characterization of m6A Modifications in Non-Clear Cell Renal Cell Carcinoma and Potential Relationship with Pathological Types.

BACKGROUND: N6-Methyladenosine (m6A) modification is a eukaryotic mRNA modification that modulates the fate of modified RNA and, therefore, the expression of proteins. m6A modifications are associated with important roles in several cancers. Most studies related to m6A modification are based on clear cell renal cell carcinoma (ccRCC) and little is known about its role in non-ccRCC. METHODS: We summarized the molecular features of different m6A modification patterns in non-ccRCC based on The Cancer Genome Atlas database and correlated them with phenotypes such as immune patterns and prognosis. We also computed the m6Ascore and assessed its prognostic value using multivariate Cox regression analysis. RESULTS: We found the immune-excluded phenotype to be predominant in non-ccRCC patients. We also found that in non-clear cell carcinoma, different m6A modification profiles determine different immune patterns and are associated with different prognosis. m6AgeneCluser typing strongly associated with pathological status. Based on our findings, we suggest that the m6Ascore can be used as an independent prognostic value for prognostic assessment in non-ccRCC. CONCLUSION: This study confirms the important role of m6A modifications in non-ccRCC, reveals the heterogeneity of tumor immunity, and highlights the promise of non-ccRCC therapy.

A prognostic risk prediction model based on ferroptosis-related long non-coding RNAs in bladder cancer: A bulk RNA-seq research and scRNA-seq validation.

BACKGROUND: To construct a prognostic risk model of bladder cancer (BC) from the perspective of long non-coding RNAs (lncRNAs) and ferroptosis, in order to guide clinical prognosis and identify potential therapeutic targets. METHODS: In-hours BC samples were collected from 4 patients diagnosed with BC, who underwent radical cystectomy. Single cell transcriptome sequencing was performed and Seurat package were used for quality control and secondary analysis. LncRNAs expression profiles of BC samples were extracted from The Cancer Genome Atlas database. And sex, age, tumor, node, metastasis stage and other clinical data was downloaded at the same time. Ferroptosis-related lncRNAs were identified by co-expression analysis. We constructed a risk model by Cox regression and least absolute shrinkage and selection operator regression analyses. The predictive strength of the risk model for overall survival (OS) of patients with BC was evaluated by the log-rank test and Kaplan-Meier method. Finally, the enrichment analysis was performed and visualized. RESULTS: We identified and included 15 prognostic ferroptosis-related lncRNAs (AL356740.1, FOXC2AS1, ZNF528AS1, LINC02535, PSMB8AS1, AL590428.1, AP000347.2, OCIAD1-AS1, AP001347.1, AC104986.2, AC018926.2, LINC00867, AC099518.4, USP30-AS1, and ARHGAP5-AS1), to build our ferroptosis-related lncRNAs risk model. Using this risk model, BC patients were divided into high and low-risk groups, and their respective survival lengths were calculated. The results showed that the OS of the low-risk group was significantly longer than that of the high-risk group. A nomogram was utilized to predict the survival rate of BC patients. As indicated in the nomogram, risk score was the most important indicator of OS in patients with BC. The ferroptosis-related lncRNAs risk model is an independent tool for prognostic risk assessment in patients with BC. Single cell transcriptome sequencing suggests that ferroptosis-related lncRNAs express specifically in BC tumor microenvironment. AL356740.1, LINC02535 and LINC00867 were mainly expressed in tumor cells. CONCLUSION: The risk model based on the ferroptosis-related lncRNAs and the genomic clinico-pathological nomogram could be used to accurately predict the prognosis of patients with BC. The lncRNAs used to build this model might become potential therapeutic targets in the future.

Prognostic Value of Genes and Immune Infiltration in Prostate Tumor Microenvironment.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers and the fifth leading cause of cancer-related death in men. Immune responses in the tumor microenvironment are hypothesized to be related to the prognosis of PCa patients; however, no studies are available to confirm the same. In this study, we aimed to explore the potential link between these two factors and identify new biomarkers to estimate the survival rate of PCa patients. METHODS: A total of 490 cases were obtained from The Cancer Genome Atlas (TCGA) database. The gene expression data were analyzed by the ESTIMATE algorithm to evaluate the immune and stromal scores. The survival rate was calculated according to the case-specific clinical data. Enrichment analysis was performed to discover the main biological processes and signaling pathways of immune responses. We further identified and analyzed hub genes in the protein-protein interaction (PPI) network and evaluated their prognostic values. RESULTS: Immune score significantly correlated with immune cell infiltration and overall survival of PCa patients. The genes CXCR4 and GPR183, identified as hub genes in the PPI network, correlated with immune cell infiltration and prognosis of PCa patients. CONCLUSION: CXCR4 and GPR183 participate in immune cell infiltration and function in PCa patients. The immune score, as well as the expression of CXCR4 and GPR183 in prostate cancer tissues, could be potential indexes for the prognosis of prostate cancer.

Potential role of CFTR in bisphenol A-induced malignant transformation of prostate cells via mitochondrial apoptosis.

Bisphenol A (BPA) is an environmental endocrine disruptor and a risk factor for prostate cancer. The cystic fibrosis transmembrane conductance regulator (CFTR) is proposed to be a prostate cancer suppressor in some recent researches. However, the potential role and mechanism of CFTR in BPA-induced prostate cancer cells has not been well identified. In this study, BPA decreased the viability of human normal prostate RWPE-1 cells detected with a CCK-8 kit. The capacity of the cell line on soft agar colony formation, wound healing, and transwell invasion indicated malignant transformation induced by BPA. Western blot analysis demonstrated that the levels of CFTR and Bcl-2 decreased, whereas Bax level increased, and ELISA detection showed a decreased ATP level in BPA-exposed cells. Cell apoptosis was analyzed with Annexin V-FITC Detection Kit by flow cytometry. However, no significant difference was observed in cell viability and apoptosis rates compared to normal RWPE-1 cells. Our research revealed a potential role of CFTR in BPA-induced malignant transformation via mitochondrial apoptosis of normal prostate cells.

Characterization of mRNA Expression and Endogenous RNA Profiles in Bladder Cancer Based on The Cancer Genome Atlas (TCGA) Database.

BACKGROUND Bladder cancer is a multifactorial disease with increasing incidence and mortality. Genetic alterations and altered expressions of mRNAs, long non-coding RNAs (lncRNAs), and miRNAs have been shown to play important roles in the tumorigenesis of bladder cancer. However, the functions of key RNAs and their regulatory network in bladder cancer are still to be elucidated. MATERIAL AND METHODS RNA profiles were downloaded from The Cancer Genome Atlas (TCGA) database. The differentially expressed mRNAs, lncRNAs, and miRNAs in bladder cancer were acquired through analyses of data from 414 bladder cancer tissues and 19 normal bladder tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed by using "DAVID6.8" and the R package "ClusterProfile". Protein-protein interaction and competing endogenous RNA (ceRNA) networks were constructed by using "STRING" database and Cytoscape 3.6.2. Based on the clinical data and Cox regression, a prognosis model was established, and survival analysis was performed. RESULTS A total of 1819 mRNAs, 659 lncRNAs, and 160 miRNAs were identified as significantly differentially expressed in bladder cancer of which 52 mRNAs, 58 lncRNAs, and 22 miRNAs were incorporated in the ceRNA network. CFL2 and TPM2 were found to be downregulated and showed significant correlation to each other in bladder cancer. HOXB5 and 6 lncRNAs (ADAMTS9-AS1, AC112721.1, LINC00460, AC110491.1, LINC00163, and HCG22) were strongly associated with high-grade, disease stages, and overall survival. CONCLUSIONS In this study, we have identified differentially expressed mRNAs, lncRNAs, and miRNAs in bladder cancer which were strongly associated with oncogenesis and prognosis. Further experimental studies are necessary to validate these results.

Knockdown of lncRNA SNHG7 inhibited cell proliferation and migration in bladder cancer through activating Wnt/ß-catenin pathway.

It is identified that long non-coding RNAs (lncRNAs) play important roles in tumorigenesis. LncRNA SNHG7 has been found to be an oncogene in varieties of tumors including bladder cancer. However, its potential regulatory mechanism in bladder cancer still remains unknown. In this study, we discovered that the expression levels of SNHG7 were significantly increased in bladder cancer tissues and cell lines. Patients with high expression level of SNHG7 suffered from poor prognosis. Additionally, knockdown of SNHG7 induced declined cell viability, proliferation as well as G0/G1 cell cycle arrest. Furthermore, we found that cell migratory ability was markedly reduced after silencing SNHG7. Next, we verified that knockdown of SNHG7 reduced the protein level of ß-catenin and thus decreased the level of its downstream targets including c-myc, cyclin D1 and E-cadherin, implying that SNHG7 might impact bladder cancer via Wnt/ß-catenin pathway. Subsequently, the rescue assays performed in SNHG7 silenced T24 cells by using activator of Wnt/ß-catenin signaling elucidated that re-activation of this pathway partly restored the inhibitory effects of SNHG7 suppression on biological behaviors of T24 cells. Collectively, SNHG7 elicited carcinogenic functions in bladder cancer partially via activating Wnt/ß-catenin signaling pathway, suggesting a potential target for the treatment and prognosis of bladder cancer.

Long non-coding RNA cartilage injury-related promotes malignancy in bladder cancer.

Recent advances have highlighted the important roles of long non-coding RNAs (lncRNAs) in a number of biological processes, including oncogenesis. However, the function of lncRNA cartilage injury-related (lncRNA-CIR) in bladder cancer progression remains elusive. A novel function for lncRNA-CIR in bladder cancer was identified in the present study. Reverse transcription quantitative polymerase chain reaction, viability, invasion assay and in vivo implantation were used to evaluate the role of lncRNA-CIR. It was identified that the expression of lncRNA-CIR was frequently upregulated in 52 cancerous tissues and selected bladder cancer cell lines. Additionally, upregulating lncRNA-CIR was demonstrated to promote viability and invasion in T24 and SW780 cells, whereas siRNA-mediated lncRNA-CIR-knockdown consistently exhibited the opposite effects. High lncRNA-CIR levels also dictated poor overall survival among patients with bladder cancer. Furthermore, in vivo implantation experiments also supported a tumorigenic function for lncRNA-CIR, as decreasing lncRNA-CIR levels markedly attenuated Ki-67 staining and xenograft tumor growth. Overall, the present study identified a novel function of lncRNA-CIR and indicates that lncRNA-CIR may serve as a potential biomarker for bladder cancer treatment.

Utility of Fluorescence In Situ Hybridization (FISH) to Sub-Classify Low-Grade Urothelial Carcinoma for Prognostication.

BACKGROUND Fluorescence in situ hybridization (FISH) is used widely to detect cancer levels, but its value in urothelial carcinoma remains unclear. The aim of this study was to use FISH to examine the urine specimens of low-grade urothelial carcinoma (UC) patients to determine the possibility of sub-classifying the prognosis of UC. MATERIAL AND METHODS We diagnosed 107 patients with low-grade UC using a UroVysion kit to detect chromosomes 3, 7, 17, and P16 in the urine. An average 46.6-month follow-up completed in January 2016 combined with the clinical follow-up data were evaluated with Spearman's correlation analysis to analyze the aberration of chromosomes in relation to the prognostication. Univariate and multivariate analysis using the Mantel-Cox log-rank test for overall, cancer-specific, and disease-free survival were used to determine the prognostic significance of CSP7/CSP17 and CSP3/GLPp16. RESULTS In the 107 samples, 84 showed positive reaction in the FISH test. Furthermore, CSP7/CSP17 was found to be significantly related with age, tumor size, T stage, and tumor numbers, but not in CSP3/GLPp16. In addition, Kaplan-Meier analysis and Cox proportional hazards regression revealed a significant negative correlation between CSP7/CSP17 and survival, while CSP3/GLPp16 showed no significantly differences. CONCLUSIONS CSP7/CSP17 positivity on FISH test appears to play a critical role in low-grade UC and may be considered as a high-risk and prognosis factor.

LncROR Promotes Bladder Cancer Cell Proliferation, Migration, and Epithelial-Mesenchymal Transition.

BACKGROUND: LncRNA ROR, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, the molecular biological function in bladder cancer has not been clearly elucidated. The aim of this study is to explore ROR expression levels and evaluated its function in bladder cancer. METHODS: LncRNA ROR expression levels in the 36 pairs of bladder cancer tissues (and corresponding non-tumor tissues) and bladder cancer cells were assessed by qRT-PCR. MTT assay, colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays, attachment/detachment and western blotting were performed to assess the effects of ROR on proliferation, apoptosis, migration/invasion and epithelial-to-mesenchymal (EMT) phenotypes in BC cells in vitro. ZEB1 is target of ROR. Rescue assays were performed to further confirm that ROR contributes to the progression of BC cells through targeting ZEB1. RESULTS: LncRNA ROR was up-regulated in bladder cancer tissues (compared to adjacent non-tumor tissues) and was almost overexpression in bladder cancer cells (compared with normal urothelial cell line SVHUC-1 cells). Increased lncRNA ROR expression significantly promoted tumor cells proliferation, inhibited cells apoptosis, facilitated cells metastasis and contributed to the formation of EMT phenotype. While down-regulated ROR could obviously inhibit cells proliferation, promote cells apoptosis, inhibit metastasis and reverse EMT to MET. ZEB1 was a target gene of ROR and was positive correlation with the level of ROR in cancer tissues. CONCLUSION: These results indicated that lncRNA ROR was associated with tumor progression in bladder cancer cells.