Comprehensive Analysis of Correlations in the Expression of miRNA Genes and Immune Checkpoint Genes in Bladder Cancer Cells

Personalised medicine is the future and hope for many patients, including those with cancers. Early detection, as well as rapid, well-selected treatment, are key factors leading to a good prognosis. MicroRNA mediated gene regulation is a promising area of development for new diagnostic and therapeutic methods, crucial for better prospects for patients. Bladder cancer is a frequent neoplasm, with high lethality and lacking modern, advanced therapeutic modalities, such as immunotherapy. MicroRNAs are involved in bladder cancer pathogenesis, proliferation, control and response to treatment, which we summarise in this perspective in response to lack of recent review publications in this field. We further performed a correlation-based analysis of microRNA and gene expression data in bladder cancer (BLCA) TCGA dataset. We identified 27 microRNAs hits with opposite expression profiles to genes involved in immune response in bladder cancer, and 24 microRNAs hits with similar expression profiles. We discuss previous studies linking the functions of these microRNAs to bladder cancer and assess if they are good candidates for personalised medicine therapeutics and diagnostics. The discussed functions include regulation of gene expression, interplay with transcription factors, response to treatment, apoptosis, cell proliferation and angiogenesis, initiation and development of cancer, genome instability and tumour-associated inflammatory reaction.

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Early and late stage MPN patients show distinct gene expression profiles in CD34+ cells

Annals of Hematology ◽

10.1007/s00277-021-04615-8 ◽

2021 ◽

Author(s):

Julian Baumeister ◽

Tiago Maié ◽

Nicolas Chatain ◽

Lin Gan ◽

Barbora Weinbergerova ◽

...

Keyword(s):

Gene Expression ◽

Late Stage ◽

Rna Splicing ◽

Bone Marrow Cells ◽

Myeloproliferative Neoplasms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Primary Myelofibrosis ◽

Estrogen Signaling ◽

Therapeutic Modalities

AbstractMyeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing–associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN. Graphical abstract

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Long non-coding RNAs in brain tumors

NAR Cancer ◽

10.1093/narcan/zcaa041 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Keisuke Katsushima ◽

George Jallo ◽

Charles G Eberhart ◽

Ranjan J Perera

Keyword(s):

Gene Expression ◽

Brain Tumors ◽

Brain Cancer ◽

Regulation Of Gene Expression ◽

Therapeutic Targets ◽

Diagnostic Biomarkers ◽

Cancer Pathogenesis ◽

Current State ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

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Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110961 ◽

2012 ◽

Vol 39 (5) ◽

pp. 916-928 ◽

Cited By ~ 20

Author(s):

BERTALAN MESKO ◽

SZILARD POLISKA ◽

SZILVIA SZAMOSI ◽

ZOLTAN SZEKANECZ ◽

JANOS PODANI ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Peripheral Blood ◽

Multiple Testing ◽

Mononuclear Cells ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Response To Treatment ◽

Peripheral Blood Mononuclear ◽

Gene Sets

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

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SMC4, CCNB1 and CKS1B as potential targets and new critical biomarkers for the prognosis of human bladder cancer

10.21203/rs.3.rs-595148/v1 ◽

2021 ◽

Author(s):

Hongpeng Fang ◽

Zhansen Huang ◽

Xianzi Zeng ◽

Jiaming Wan ◽

Jieying Wu ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Gene Expression Omnibus ◽

Transcriptional Level ◽

Hub Genes ◽

Kaplan Meier ◽

High Form

Abstract Background As a common malignant cancer of the urinary system, the precise molecular mechanisms of bladder cancer remain to be illuminated. The purpose of this study was to identify core genes with prognostic value as potential oncogenes for the diagnosis, prognosis or novel therapeutic targets of bladder cancer. Methods The gene expression profiles GSE3167 and GSE7476 were available from the Gene Expression Omnibus (GEO) database. Next, PPI network was built to filter the hub gene through the STRING database and Cytoscape software and GEPIA and Kaplan-Meier plotter were implemented. Frequency and type of hub genes and sub groups analysis were performed in cBioportal and ULCAN database. Finally,We used RT-qPCR to confirm our results. Results Totally, 251 DEGs were excavated from two datasets in our study. We only founded high expression of SMC4, TYMS, CCNB1, CKS1B, NUSAP1 and KPNA2 was associated with worse outcomes in bladder cancer patients and no matter from the type of mutation or at the transcriptional level of hub genes, the tumor showed a high form of expression. However, only the expression of SMC4,CCNB1and CKS1B remained changed between the cancer and the normal samples in our results of RT-qPCR. Conclusion In conclusion,These findings indicate that the SMC4,CCNB1 and CKS1B may serve as critical biomarkers in the development and poor prognosis.

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Genetic and epigenetic architecture of sex-biased expression in the jewel wasps Nasonia vitripennis and giraulti

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1510338112 ◽

2015 ◽

Vol 112 (27) ◽

pp. E3545-E3554 ◽

Cited By ~ 34

Author(s):

Xu Wang ◽

John H. Werren ◽

Andrew G. Clark

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Regulation Of Gene Expression ◽

Sequence Divergence ◽

Adult Males ◽

Rna Seq ◽

Functional Categories ◽

Nasonia Vitripennis ◽

Constitutive Gene Expression ◽

Genome Bisulfite Sequencing

There is extraordinary diversity in sexual dimorphism (SD) among animals, but little is known about its epigenetic basis. To study the epigenetic architecture of SD in a haplodiploid system, we performed RNA-seq and whole-genome bisulfite sequencing of adult females and males from two closely related parasitoid wasps, Nasonia vitripennis and Nasonia giraulti. More than 75% of expressed genes displayed significantly sex-biased expression. As a consequence, expression profiles are more similar between species within each sex than between sexes within each species. Furthermore, extremely male- and female-biased genes are enriched for totally different functional categories: male-biased genes for key enzymes in sex-pheromone synthesis and female-biased genes for genes involved in epigenetic regulation of gene expression. Remarkably, just 70 highly expressed, extremely male-biased genes account for 10% of all transcripts in adult males. Unlike expression profiles, DNA methylomes are highly similar between sexes within species, with no consistent sex differences in methylation found. Therefore, methylation changes cannot explain the extensive level of sex-biased gene expression observed. Female-biased genes have smaller sequence divergence between species, higher conservation to other hymenopterans, and a broader expression range across development. Overall, female-biased genes have been recruited from genes with more conserved and broadly expressing “house-keeping” functions, whereas male-biased genes are more recently evolved and are predominately testis specific. In summary, Nasonia accomplish a striking degree of sex-biased expression without sex chromosomes or epigenetic differences in methylation. We propose that methylation provides a general signal for constitutive gene expression, whereas other sex-specific signals cause sex-biased gene expression.

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Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1912459116 ◽

2019 ◽

Vol 116 (39) ◽

pp. 19490-19499 ◽

Cited By ~ 76

Author(s):

Chenglong Xia ◽

Jean Fan ◽

George Emanuel ◽

Junjie Hao ◽

Xiaowei Zhuang

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Spatial Information ◽

Detection Efficiency ◽

Expression Profiles ◽

Regulation Of Gene Expression ◽

Rna Profiling ◽

Spatially Resolved ◽

Cycle Dependent

The expression profiles and spatial distributions of RNAs regulate many cellular functions. Image-based transcriptomic approaches provide powerful means to measure both expression and spatial information of RNAs in individual cells within their native environment. Among these approaches, multiplexed error-robust fluorescence in situ hybridization (MERFISH) has achieved spatially resolved RNA quantification at transcriptome scale by massively multiplexing single-molecule FISH measurements. Here, we increased the gene throughput of MERFISH and demonstrated simultaneous measurements of RNA transcripts from ∼10,000 genes in individual cells with ∼80% detection efficiency and ∼4% misidentification rate. We combined MERFISH with cellular structure imaging to determine subcellular compartmentalization of RNAs. We validated this approach by showing enrichment of secretome transcripts at the endoplasmic reticulum, and further revealed enrichment of long noncoding RNAs, RNAs with retained introns, and a subgroup of protein-coding mRNAs in the cell nucleus. Leveraging spatially resolved RNA profiling, we developed an approach to determine RNA velocity in situ using the balance of nuclear versus cytoplasmic RNA counts. We applied this approach to infer pseudotime ordering of cells and identified cells at different cell-cycle states, revealing ∼1,600 genes with putative cell cycle-dependent expression and a gradual transcription profile change as cells progress through cell-cycle stages. Our analysis further revealed cell cycle-dependent and cell cycle-independent spatial heterogeneity of transcriptionally distinct cells. We envision that the ability to perform spatially resolved, genome-wide RNA profiling with high detection efficiency and accuracy by MERFISH could help address a wide array of questions ranging from the regulation of gene expression in cells to the development of cell fate and organization in tissues.

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Alkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression

Nature Communications ◽

10.1038/s41467-019-13394-w ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Nicola P. Montaldo ◽

Diana L. Bordin ◽

Alessandro Brambilla ◽

Marcel Rösinger ◽

Sarah L. Fordyce Martin ◽

...

Keyword(s):

Gene Expression ◽

Genome Stability ◽

Genome Instability ◽

Excision Repair ◽

Regulation Of Gene Expression ◽

Direct Interaction ◽

Dna Glycosylase ◽

Pol Ii ◽

Naked Dna ◽

Alkyladenine Dna Glycosylase

AbstractBase excision repair (BER) initiated by alkyladenine DNA glycosylase (AAG) is essential for removal of aberrantly methylated DNA bases. Genome instability and accumulation of aberrant bases accompany multiple diseases, including cancer and neurological disorders. While BER is well studied on naked DNA, it remains unclear how BER efficiently operates on chromatin. Here, we show that AAG binds to chromatin and forms complex with RNA polymerase (pol) II. This occurs through direct interaction with Elongator and results in transcriptional co-regulation. Importantly, at co-regulated genes, aberrantly methylated bases accumulate towards the 3′end in regions enriched for BER enzymes AAG and APE1, Elongator and active RNA pol II. Active transcription and functional Elongator are further crucial to ensure efficient BER, by promoting AAG and APE1 chromatin recruitment. Our findings provide insights into genome stability maintenance in actively transcribing chromatin and reveal roles of aberrantly methylated bases in regulation of gene expression.

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Partially Degraded RNA from Bladder Washing is a Suitable Sample for Studying Gene Expression Profiles in Bladder Cancer

European Urology ◽

10.1016/j.eururo.2006.05.039 ◽

2006 ◽

Vol 50 (6) ◽

pp. 1347-1356 ◽

Cited By ~ 12

Author(s):

Lourdes Mengual ◽

Moisès Burset ◽

Elisabet Ars ◽

María José Ribal ◽

Juan José Lozano ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Expression Profiles ◽

Gene Expression Profiles

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Gene expression profiling in bladder cancer to identify potential therapeutic targets.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4518 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4518-4518

Author(s):

Syed A. Hussain ◽

Daniel H. Palmer ◽

Wing Kin Syn ◽

Joseph J Sacco ◽

Bryony Lloyd ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Hierarchical Clustering ◽

Expression Profiles ◽

Expression Patterns ◽

Invasive Cancer ◽

Classical Complement Pathway ◽

Grade 3 ◽

Muscle Invasive

4518 Background: Characterization of gene expression patterns in bladder cancer (BC) allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Methods: Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Results: Hierarchical clustering defined signatures, which differentiated between cancer and normal, muscle-invasive or non-muscle invasive cancer and normal, g1 and g3. Pathways associated with cell cycle and proliferations were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer as compared to normal tissue. Conclusions: This study contributes to a growing body of work on gene expression signatures in BC. The data support an important role for osteopontin in BC, and identify several pathways worthy of further investigation. [Table: see text]

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The efficacy of trimodal chemoradiotherapy with gemcitabine and cisplatin as a bladder-preserving strategy for the treatment of muscle invasive bladder cancer: A single-arm prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.516 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 516-516

Author(s):

Hiroaki Matsumoto ◽

Kazuhiro Nagao ◽

Sho Ozawa ◽

Masahiro Samoto ◽

Junichi Mori ◽

...

Keyword(s):

Bladder Cancer ◽

Clinical Stage ◽

Good Prognosis ◽

Response To Treatment ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Bladder Preservation ◽

Cancer Specific Survival ◽

Free Survival ◽

Muscle Invasive

516 Background: Radical cystectomy is still the standard treatment for muscle-invasive bladder cancer (MIBC), while the patients with MIBC are not always appropriate candidates due to multiple comorbidities. We establish novel treatment strategy by trimodal treatment. Methods: The regimen was gemcitabine 300 mg/m2, and cisplatin 30mg/m2 in day 1 and concomitant irradiation 2Gy/Fr, 5 fraction per week. Irradiation was administered to whole pelvis up to 30Gy, then boost to true pelvis until total 48Gy to 54Gy. Extensive transurethral resection (TURBT) was performed and we confirmed pathological stage ≥T2. TURBT was also performed after chemoradiotherapy to evaluate the pathological response to treatment. This study was approved in our institutional review board (ID: H23-89) and the information was opened on UMIN (ID: UMIN000006363). We analyzed their treatment efficacy and survival. Results: The patients were 29 men and 9 women, median age was 76.5 y.o. and median follow up was 23 months (1 - 112). Clinical stage T2, T3, T4, N1 and N2 were 23, 10, 5, 4, 2 cases, respectively. The 2- and 5-year metastatic-free survival (MFS), bladder-recurrence free survival (bRFS), cancer-specific survival (CSS), and overall survival (OS) rates after treatment were 91.7 and 84.0%, 59.7 and 42.6%, 87.3 and 87.3%, and 87.3 and 81.8%, respectively. Salvage cystectomy was performed 3 patients and they were still alive. CR rate was 78.9% and overall response rate was 92.1%. cT stage and valiant histology was not associated with treatment response. The patients achieved CR had significant good prognosis in CSS (p=0.0149) and OS (p=0.0149) compared with non-responders. In cox hazard model, CR achievement was significant prognostic factors for OS (p =0.0015, HR 6.804e+26, 95% CI 56.94-1.631e+86). Patients were able to receive 3 to 5 cycle GC radiation and any grade 3 or more adverse event was 7 (18.4%) cases. no treatment related death was recorded. Conclusions: In selected patients, GC radiation for MIBC may provide good oncological outcomes as bladder preservation strategy.

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