Dataset Information

Association between chromosomal aberration of exfoliated bladder cells in the urine and oxidative stress in patients with bladder transitional cell carcinoma.

ABSTRACT: The aim of the current study was to investigate the chromosomal aberrations of exfoliated bladder cells in the urine and blood oxidative stress in patients with bladder transitional cell carcinoma (BTCC). A total of 40 healthy controls and 246 patients with BTCC were recruited. Abnormal levels of CSP3, CSP7, CSP17 and GLPp16 were detected by fluorescence in situ hybridization (FISH) in exfoliated bladder cells in the urine of patients with BTCC. Serum total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured. Significant differences were observed in the abnormal CSP3, CSP7, CSP17, GLPp16 signals and FISH positive rate between patients with BTCC and healthy controls (P<0.001). Serum TOS, TAS and OSI were also significantly different between the two groups (P<0.001). The clinical stage of BTCC was not associated with abnormal CSP3, CSP7, CSP17, GLPp16 or FISH positive rate and oxidative stress (P>0.05). A Gamma rank correlation analysis revealed an association between the pathological grade of BTCC with abnormal CSP3, CSP7 and CSP17 as well as FISH positive rate (P<0.001). In addition, the clinical stage of BTCC was associated with serum TOS, TAS and OSI (P<0.001). Evaluation of the association between chromosomal aberrations and oxidative stress revealed that abnormal CSP3, CSP7 and CSP17 were positively associated with serum TOS and OSI (P<0.001), abnormal CSP7 and CSP17 were negatively associated with serum TAS (P<0.001), but abnormal GLPp16 was not associated with serum TOS, TAS or OSI (P>0.05). Therefore, the chromosomal aberrations of exfoliated bladder cells in the urine are associated with blood oxidative stress in patients with BTCC, and these factors may contribute to the occurrence and development of BTCC.

SUBMITTER: Wang D

PROVIDER: S-EPMC5494805 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundGenetic aberrations have been identified in nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains elusive. There are increasing evidences that the apoptotic nuclease caspase-activated deoxyribonuclease (CAD) is one of the players leading to translocation in leukemia. Oxidative stress, which has been strongly implicated in carcinogenesis, is a potent apoptotic inducer. Most of the NPC etiological factors are known to induce oxidative stress. Although apoptosis is a cell death process, cells possess the potential to survive apoptosis upon DNA repair. Eventually, the surviving cells may carry rearranged chromosomes. We hypothesized that oxidative stress-induced apoptosis may cause chromosomal breaks mediated by CAD. Upon erroneous DNA repair, cells that survive apoptosis may harbor chromosomal rearrangements contributing to NPC pathogenesis. This study focused on the AF9 gene at 9p22, a common deletion region in NPC. We aimed to propose a possible model for molecular mechanism underlying the chromosomal rearrangements in NPC.ResultsIn the present study, we showed that hydrogen peroxide (H2O2) induced apoptosis in NPC (HK1) and normal nasopharyngeal epithelial (NP69) cells, as evaluated by flow cytometric analyses. Activity of caspases 3/7 was detected in H2O2-treated cells. This activity was inhibited by caspase inhibitor (CI). By nested inverse polymerase chain reaction (IPCR), we demonstrated that oxidative stress-induced apoptosis in HK1 and NP69 cells resulted in cleavages within the breakpoint cluster region (BCR) of the AF9 gene. The gene cleavage frequency detected in the H2O2-treated cells was found to be significantly higher than untreated control. We further found that treatment with CI, which indirectly inhibits CAD, significantly reduced the chromosomal breaks in H2O2-cotreated cells. Intriguingly, a few breakpoints were mapped within the AF9 region that was previously reported to translocate with the mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemia (ALL) patient.ConclusionsIn conclusion, our findings suggested that oxidative stress-induced apoptosis could be one of the mechanisms underlying the chromosomal rearrangements in NPC. CAD may play an important role in chromosomal cleavages mediated by oxidative stress-induced apoptosis. A potential model for oxidative stress-induced apoptosis mediating chromosomal rearrangements in NPC is proposed.

Project description:PurposeUveal melanoma is the most common intraocular primary tumor, involving iris, ciliary body and choroid. More than 90% of the patients develop hepatic metastasis with an average survival time of 7 months. We have used formalin fixed paraffin embedded sections to validate the presence of monosomy 3, an accurate predictor of metastasis, chromosome 8 isochromosome (8q22), and 1p36 deletion. This study also tested the presence of oncomirs in uveal melanoma samples by microRNA (miRNA) expression profiling.MethodsChromogenic in situ hybridization (CISH) was performed in formalin fixed, paraffin embedded sections of uveal melanoma to analyze chromosome 1, 3, and 8 aberrations (n=60). MicroRNA (miRNA) expression profiling was done on paraffin sections of invasive tumor with liver metastasis (n=1) and non invasive tumor (n=1) in biological duplicates. Samples for miRNA expression profiling were identified based on case registry and the harboring of monosomy 3 by CISH.ResultsA significant correlation (p=0.05) between metastasizing and non-metastasizing melanoma harboring chromosomal aberrations- monosomy3, c-myc, and 1p36 was observed by Pearson's correlation. A significant correlation was observed in monosomy 3 and 1p36 positive cases in the tumor samples (p=0.039). No significance was observed between monosomy 3 and c-myc positive cases. No significance (p=0.096) was observed between c-myc amplification and trisomy (extra whole chromosome 8). MicroRNA expression profiling revealed the presence of 19 miRNAs expressed in non-metastasizing melanoma and absent in metastasizing melanoma. Eleven miRNAs were found to be expressed in metastasizing melanoma and absent in non-metastasizing melanoma. Genes targeted by the miRNAs were found to be present in chromosomal regions 8p22, 13q, and 17p but were often found to be deleted.ConclusionsThis technique can be applied to routine pathology using archival specimens to identify patients with monosomy 3. We were able to perform CISH in all the cases except the heavily pigmented tumors, where dots were observed but were not assessed. Initial studies on microRNA have revealed their role as oncomirs in both metastasizing and non-metastasizing melanomas. Further studies may provide insights into their role in tumor progression and facilitate metastatic phenotype analysis.

Dataset Information

Association between chromosomal aberration of exfoliated bladder cells in the urine and oxidative stress in patients with bladder transitional cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets