Tobacco smoking transcriptional imprinting contributes to urothelial cancer
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ABSTRACT: Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours. we used microarray techniques to define gene expression profile which may explain the contribution of smoking to urothelial carcinoma. Gene expression profiling using GeneChip HG-U133A Plus 2.0 (Affymetrix) was performed on non-malignant and carcinogenic urothelium from six patients with superficial and six with invasive urothelial carcinoma, each group including two current, former, and non-smokers.
Project description:Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours. we used microarray techniques to define gene expression profile which may explain the contribution of smoking to urothelial carcinoma.
Project description:Activation of oncogenic ras pathway accounts for up to 90% low-grade superficial urothelial carcinomas of bladder, and p53 deficiency is very common in high-grade muscle invasive carcinomas. These two pathways in bladder urothelial tumorigenesis used to be considered divergent and their potential collaboration has not been illustrated. We did laser capture micro-dissection (LCM) to separate the tumor cells from the whole bladder tissues from H-ras transgenic and p53 knockout mice, as well as normal urothelial cells as control. Microarray was then performed to identify distinct classes of up-regulated genes during tumorigenesis and progression. In order to get the gene expression profiles of carcinoma in situ (CIS), muscle invasive tumors and normal cells, we used LCM to purify the cells from mixture of different types of cells, and then extracted RNA for microarray. There are three groups applied in microarray, which are normal cells as control, CIS (tumor genesis) and invasive tumors (tumor progression).
Project description:It is unclear how urothelial carcinoma of the urinary bladder change, genetically and phenotypically, as patients progress from recurrent non muscle-invasive (NMI) to muscle-invasive (MI) disease or disease that require radical cystectomy. This data set contains gene expression data from 200 samples in a longitudinal study of such patients. Overlap with previously GEO-published cohorts from our lab is described in the metadata.
Project description:This study used non-invasive sampling by tape-stripping coupled with data-independent acquisition mass spectrometry (DIA-MS) proteomics to profile the proteome of 61 histopathologically diagnosed Keratinocytic skin lesions (KSLs), including pre-malignant actinic keratosis (AK) and Bowen's disease (BD), and invasive cutaneous squamous cell carcinoma (cSCC)as well as matched normal stratum corneum samples collected from 26 patients.
Project description:As various data suggest that lncRNAs are important in human cancer, we hypothesized that they play a role in urothelial carcinogenesis. To test this hypothesis we analysed 83 normal and malignant urothelial samples using NCodeM-bM-^DM-" Human Non-coding RNA Microarrays for differentially expressed lncRNAs with potential regulatory functions in urothelial cell cancer (UCC). We identified global changes in lncRNA expression that reflect the disease phenotype. We then performed explorative analysis (siRNA gene knock-down and loss-of-function studies) of selected species and identified those with potential prognostic roles. Quantitative real-time PCR was used to validate the microarray findings. Total RNA was extracted from urothelial samples from 57 patients with UCC (23 low-grade NMI, 14 high-grade NMI and 20 invasive tumours) and from 26 disease free controls.
Project description:Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide including the Asian subcontinent. Oral carcinoma exhibits inherent heterogeneity in terms of the sites involved, etiology and pathology. They occur at multiple sites such as tongue, buccal mucosa, maxilla. Effective approaches towards improving survival rates in OSCC patients are primarily focused on early detection of the disease. The early clinical indication of the disease follows the development of potentially malignant lesions (leukoplakia/erythro-leukoplakia) with varied rates of transformation. Currently histopathological evaluation of oral biopsy is generally practiced to evaluate potential malignancy. However, human saliva has been considered to be a valuable medium for discovering biomarker molecules for malignancy. Exfoliated cancer cells may release protein or RNA molecules into the saliva or free molecules may be secreted or leaked from cancer cells representing gene expression changes associated with tumor development. Salivary proteins thus provide a strong option for development of non-invasive, point-of-care assays for screening/early detection of oral cancers. Dysplastic leukoplakia (LP) of the oral cavity is a potentially malignant condition for oral squamous cell carcinoma (OSCC), early detection of which is an unmet clinical need. In an effort to develop non-invasive biomarker based method for early detection of the disease, we have used quantitative mass spectrometry to identify differently abundant salivary proteins in OSCC (buccal mucosa) patients and individuals with potential to develop cancer (oral dysplastic leukoplakia) in comparison to healthy controls (with risk habits such as tobacco chewing or smoking).
Project description:In this study, we investigated the changes in phosphorylation of proteins in urinary extracellular vesicles from dogs with invasive urothelial carcinoma compared to control dogs.
Project description:Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer. Affymetrix CytoScan HD Arrays were performed according to the manufacturer's directions on genomic DNA extracted directly from 12 snap-frozen human urothelial carcinoma primary tumors with somatic mutations of the STAG2 gene.