Gene expression profile and enrichment pathways in different stages of bladder cancer

Fang, Zhen; Zang, Wen; Chen, R.; Ye, B.-W.; Wang, X.-W.; Yi, Suhong; Chen, W.; He, Feng; Ye, G.

doi:10.4238/2013.may.6.1

Cited by 57 publications

(46 citation statements)

References 40 publications

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“…The finding that OPN expression was strikingly upregulated (>10-fold) in invasive bladder cancers compared with the healthy tissue is consistent with previous studies demonstrating upregulation of OPN in urothelial malignancy (22,26–28). Whilst OPN RNA expression data is well represented in BC tissue (28,29), protein expression data are limited (26,27). Therefore, OPN expression was examined between MIBC and healthy urothelium to determine whether commonality between RNA and protein expression exists in BC.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in bladder cancer identifies potential therapeutic targets

Hussain

Palmer

Syn

et al. 2017

International Journal of Oncology

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Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. 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. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation 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 compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling in bladder cancer identifies potential therapeutic targets

Hussain

Palmer

Syn

et al. 2017

International Journal of Oncology

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“…While these databases provide data from various tumors, none of these databases have published gene expression data from bladder cancer or IL-4R α expression. Whole-genome sequencing of tumors and matched normal samples focused on 18,091 genes in urothelial cancers, but it did not include IL-4R α [ 32 , 34 ]. Additional data analysis of RNA-seq results from a TCGA subset of 230 bladder cancer specimens by GenePool program largely confirmed our RT-PCR and IHC results for all three chains of IL-4R.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease

et al. 2014

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Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran–Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III–IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not expressed. Ten normal bladder specimens demonstrated ≤1+ staining for IL-4Rα and IL-13Rα1 and no staining for IL-2RγC. These results demonstrate that IL-4Rα is overexpressed in human bladder cancer, which correlates with advanced grade and stage of the disease. Thus, IL-4Rα may be a bladder tumor-associated protein and a prognostic biomarker.

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“…The functions of these target genes were associated with the following biological processes: 'Signal transduction', 'cell adhesion and migration', 'cell proliferation', 'inflammatory cell infiltration', 'angiogenesis' and 'immunoregulation'. Additionally, various pathways and target genes were associated with the development and progression of several other human cancer types (21)(22)(23). The present results indicate that the three aforementioned pathways, and 14 identified genes, may represent key regulators of NPC tumorigenesis.…”

Section: Discussionmentioning

confidence: 55%

Integrated analysis of transcriptome profiling predicts potential lncRNA and circRNA targets in human nasopharyngeal carcinoma

Zhou

Qiu

et al. 2020

Oncol Lett

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Non-coding RNAs (ncRNAs) regulate numerous genes and influence the progression of various human diseases, including cancer. The role of regulatory ncRNAs implicated in nasopharyngeal carcinoma (NPC), as well as their target genes, remains unclear. The present study aimed to investigate specific long non-coding (lnc)RNAs, circular RNAs (circRNAs) and mRNAs associated with the molecular pathogenesis of NPC, and to predict the underlying target genes of specific lncRNAs and circRNAs. The expression levels of lncRNAs, circRNAs and mRNAs in NPC and chronic nasopharyngitis tissues were detected and analyzed using microarray and bioinformatics techniques. A total of 2.80% lncRNAs (425 upregulated and 431 downregulated) were significantly differentially expressed (DE) between the two tissue types. Additionally, 0.96% circRNAs (18 upregulated and 13 downregulated) were significantly DE, while 2.94% mRNAs (426 upregulated and 341 downregulated) were significantly DE between the two tissue types. In total, 420 NPC-associated nearby encoding genes (196 up-and 224 downregulated) of the DE lncRNAs were identified. Overlap analysis identified 23 DE circRNAs and their corresponding target genes, with 37 microRNAs and 50 mRNAs, from which 14 interaction networks were constructed. Subsequent pathway analysis revealed 221 DE target genes corresponding to 31 key signaling pathways associated with NPC, 14 of which may represent hub genes associated with NPC pathophysiology. Thus, certain lncRNAs, circRNAs and mRNAs are aberrantly expressed in NPC tissues, and partially specific lncRNAs, circRNAs and their target genes may influence the tumorigenesis and progression of NPC. Target prediction and regulatory network identification may help to determine the pathogenic mechanisms of NPC.

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Gene expression profile and enrichment pathways in different stages of bladder cancer

Cited by 57 publications

References 40 publications

Gene expression profiling in bladder cancer identifies potential therapeutic targets

Gene expression profiling in bladder cancer identifies potential therapeutic targets

Interleukin‐4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease

Integrated analysis of transcriptome profiling predicts potential lncRNA and circRNA targets in human nasopharyngeal carcinoma

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