Dataset Information

Common Core Bacterial Biomarkers of Bladder Cancer Based on Multiple Datasets.

ABSTRACT: Recent studies have shown that microorganisms may be associated with the onset and development of bladder cancer. The purpose of this study is to identify the common core bacteria associated with bladder cancer. We characterized the urinary microbial profile of the individuals with bladder cancer by 16S rRNA gene sequencing, and the results of 24 bladder cancer samples collected in our laboratory reveal 31 common core bacteria at genera level. In addition, the abundance of four common core bacteria is significantly higher in bladder cancer samples than in samples from nondiseased people analyzed by LEfSe, based on two previous datasets. In particular, the abundance of Acinetobacter is much higher in bladder cancer samples. It has been reported that Acinetobacter is involved not only in biofilm formation but also in the adhesion and invasion of epithelial cells, the spread of bacteria caused by the degradation of phospholipids in the mucosal barrier, and the escape of the host immune response. Thus, Acinetobacter may be related to bladder cancer and is a potential microbial marker of bladder cancer. However, due to the limited number of participants, further studies are needed to better understand the role of microorganisms in bladder cancer to provide novel biomarkers for diagnosis, prognosis, and therapy.

SUBMITTER: Mai G

PROVIDER: S-EPMC6607711 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Common Core Bacterial Biomarkers of Bladder Cancer Based on Multiple Datasets.

Mai Guoqin G Chen Limei L Li Ran R Liu Quan Q Zhang Haoran H Ma Yingfei Y

BioMed research international 20190619

Recent studies have shown that microorganisms may be associated with the onset and development of bladder cancer. The purpose of this study is to identify the common core bacteria associated with bladder cancer. We characterized the urinary microbial profile of the individuals with bladder cancer by 16S rRNA gene sequencing, and the results of 24 bladder cancer samples collected in our laboratory reveal 31 common core bacteria at genera level. In addition, the abundance of four common core bacte ...[more]

PMID: 31321235

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Project description:BACKGROUND:Accumulating emerging studies have demonstrated that systemic inflammation can obviously affect tumor occurrence and progression. Nevertheless, the prognostic value of hematological inflammation biomarkers in bladder cancer is controversial. Thus, we conducted a meta-analysis to evaluate the key hematological biomarkers with various clinical outcomes in bladder cancer. METHODS:We used online databases PUBMED and EMBASE to search relevant studies published prior to August 2019. After collecting the basic characteristics and prognostic data from the studies included, overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were used as primary results. Subgroup analyses were performed according to ethnicity, the number of samples, survival outcomes, the value of cut-off, follow-up time and metastasis stage. RESULTS:Thirty-three independent studies with 17,087 bladder cancer patients were added in the present analysis. The collected results showed that the increased neutrophil-to-lymphocyte ratio was associated with a poor OS (hazard ratio [HR]?=?1.48, 95% confidence interval [CI]: 1.32-1.67, P?<?.00001), CSS (HR?=?1.71, 95%CI: 1.35-2.18, P?<?.0001) and PFS (HR?=?1.59, 95%CI: 1.38-1.83, P?<?.00001). Additionally, the elevated platelet-to-lymphocyte ratio was related to a poor OS (HR?=?1.29, 95% CI: 1.07-1.54, P?=?.007), CSS (HR?=?1.14, 95%CI?=?0.98-1.34, P?=?.02) and PFS (HR?=?1.2, 95%CI: 1.08-1.34, P?=?.0008). Moreover, a decreased lymphocyte-to-monocyte ratio was associated with a poor OS (HR?=?0.77, 95% CI: 0.70-0.84, P?=?.001), CSS (HR?=?0.76, 95%CI: 0.70-0.84). An elevated modified Glasgow prognostic score was also associated with a poor OS (HR?=?2.71, 95%CI: 1.08-2.82, P?=?.003), CSS (HR?=?1.50, 95%CI: 0.56-4.05) and PFS (HR?=?1.52, 95%CI: 1.23-1.88, P?=?.001). CONCLUSIONS:Our study indicated that the pretreatment hematological biomarkers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and modified Glasgow prognostic score) were predicative biomarkers of prognosis in bladder cancer patients. Further research is needed to conduct further prospective and multicenter studies to confirm our findings.

Project description:Background: Clinical outcomes of bladder cancer (BC) are tightly associated with the stage and grade of the initial diagnosis of BC because early detection is clearly important for patients with BC. However, the diagnostic capability of current detection methods, such as urinary cytology, cystoscopy, imageology method, and several urine-based tests, is inadequate for early detection of BC. The objective of our study is to discover novel biomarkers for detecting BC at an early stage, called non-muscle invasive (NMI) BC, using liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based metabolomics. Methods: First, morning midstream urine samples were collected from healthy adult and NMIBC patients. The LC-HRMS-based metabolomics were applied to distinguish the NMIBC group without hematuria from the controls (gender- and age-matched volunteers with normal clinically healthy index), low-grade NMIBC from the controls, and high-grade from low-grade NMIBC. Results: A total of 284 subjects were enrolled in our study including 117 healthy adults, 80 NMIBC patients without hematuria, and 87 NMIBC patients with hematuria. The metabolite panel including dopamine 4-sulfate, MG00/1846Z,9Z,12Z,15Z/00, aspartyl-histidine, and tyrosyl-methionine was found in a discovery set, which showed the predictive ability to distinguish the NMIBC group from the control group with an area under the curve (AUC) of 0.838 in an external validation set. The AUC of the panel for low-grade NMIBC samples, which consisted of 3-hydroxy-cis-5-tetradecenoylcarnitine, 6-ketoestriol, beta-cortolone, tetrahydrocorticosterone, and heptylmalonic acid, was 0.899. The sensitivity and specificity were 0.881 and 0.786, respectively. The AUC of the panel for distinction of low-grade NMIBC with and without hematuria against high-grade NMIBC with and without hematuria were 0.827 and 0.755, respectively. In addition, metabolites involved in tryptophan metabolism were upregulated in the urine of high-grade NMIBC patients when compared with low-grade NMIBC patients with the presence or absence of hematuria. Conclusion: The NMIBC urine metabolic profiling was able to assist in the early detection of BC. Panels of metabolites were discovered to have a potential value for high-grade NMIBC and low-grade NMIBC diagnosis as well as for NMIBC grading distinction.

Project description:Background:The molecular mechanisms and genetic markers of thyroid cancer are unclear. In this study, we used bioinformatics to screen for key genes and pathways associated with thyroid cancer development and to reveal its potential molecular mechanisms. Methods:The GSE3467, GSE3678, GSE33630, and GSE53157 expression profiles downloaded from the Gene Expression Omnibus database (GEO) contained a total of 164 tissue samples (64 normal thyroid tissue samples and 100 thyroid cancer samples). The four datasets were integrated and analyzed by the RobustRankAggreg (RRA) method to obtain differentially expressed genes (DEGs). Using these DEGs, we performed gene ontology (GO) functional annotation, pathway analysis, protein-protein interaction (PPI) analysis and survival analysis. Then, CMap was used to identify the candidate small molecules that might reverse thyroid cancer gene expression. Results:By integrating the four datasets, 330 DEGs, including 154 upregulated and 176 downregulated genes, were identified. GO analysis showed that the upregulated genes were mainly involved in extracellular region, extracellular exosome, and heparin binding. The downregulated genes were mainly concentrated in thyroid hormone generation and proteinaceous extracellular matrix. Pathway analysis showed that the upregulated DEGs were mainly attached to ECM-receptor interaction, p53 signaling pathway, and TGF-beta signaling pathway. Downregulation of DEGs was mainly involved in tyrosine metabolism, mineral absorption, and thyroxine biosynthesis. Among the top 30 hub genes obtained in PPI network, the expression levels of FN1, NMU, CHRDL1, GNAI1, ITGA2, GNA14 and AVPR1A were associated with the prognosis of thyroid cancer. Finally, four small molecules that could reverse the gene expression induced by thyroid cancer, namely ikarugamycin, adrenosterone, hexamethonium bromide and clofazimine, were obtained in the CMap database. Conclusion:The identification of the key genes and pathways enhances the understanding of the molecular mechanisms for thyroid cancer. In addition, these key genes may be potential therapeutic targets and biomarkers for the treatment of thyroid cancer.

Project description:BACKGROUND:Multiple myeloma is a cancer which has a high occurrence rate and causes great injury to people worldwide. In recent years, many studies reported the effects of miRNA on the appearance of multiple myeloma. However, due to the differences of samples and sequencing platforms, a large number of inconsistent results have been generated among these studies, which limited the cure of multiple myeloma at the miRNA level. METHODS:We performed meta-analyses to identify the key miRNA biomarkers which could be applied on the treatment of multiple myeloma. The key miRNAs were determined by overlap comparisons of seven datasets in multiple myeloma. Then, the target genes for key miRNAs were predicted by the software TargetScan. Additionally, functional enrichments and binding TFs were investigated by DAVID database and Tfacts database, respectively. RESULTS:Firstly, comparing the normal tissues, 13 miRNAs were differently expressed miRNAs (DEMs) for at least three datasets. They were considered as key miRNAs, with 12 up-regulated (hsa-miR-106b, hsa-miR-125b, hsa-miR-130b, hsa-miR-138, hsa-miR-15b, hsa-miR-181a, hsa-miR-183, hsa-miR-191, hsa-miR-19a, hsa-miR-20a, hsa-miR-221 and hsa-miR-25) and one down-regulated (hsa-miR-223). Secondly, functional enrichment analyses indicated that target genes of the upregulated miRNAs were mainly transcript factors and enriched in transcription regulation. Besides, these genes were enriched in multiple pathways: the cancer signal pathway, insulin signal metabolic pathway, cell binding molecules, melanin generation, long-term regression and P53 signaling pathway. However, no significant enrichment was found for target genes of the down-regulated genes. Due to the distinct regulation function, four miRNAs (hsa-miR-19a has-miR-221 has-miR25 and has-miR223) were ascertained as the potential prognostic and diagnostic markers in MM. Thirdly, transcript factors analysis unveiled that there were 148 TFs and 60 TFs which bind target genes of the up-regulated miRNAs and target genes of the down-regulated miRNAs, respectively. They respectively generated 652 and 139 reactions of TFs and target genes. Additionally, 50 (31.6%) TFs were shared, while higher specificity was found in TFs of target genes for the upregulated miRNAs. DISCUSSIONS:Together, our findings provided the key miRNAs which affected occurrence of multiple myeloma and regulation function of these miRNAs. It is valuable for the prognosis and diagnosis of multiple myeloma.

Project description:IntroductionBladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary-based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer.ResultsSENSITIVITY AND SPECIFICITY RANGES, RESPECTIVELY, FOR EACH MARKER WERE REPORTED AS FOLLOWS: BTA Stat (Polymedco), 52.5%-78.0% and 69.0%-87.1%; BTA Trak (Polymedco), 51%-100% and 73%-92.5%; cytology, 12.1%-84.6% and 78.0%-100%; hematuria dipstick, 47.0%-92.6% and 51.0%-84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%-100% and 60.0%-95.0%; NMP22 BladderChek (Matritech), 49.5%-65.0% and 40.0%-89.8%; ImmunoCyt/uCyt+ (DiagnoCure), 63.3%-84.9% and 62.0%-78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%-89.3% and 61.0%-77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%-100% and 65.0%-96.0%.ConclusionWe find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers, alone or in panel, would best accomplish this.

Dataset Information

Common Core Bacterial Biomarkers of Bladder Cancer Based on Multiple Datasets.

Publications

Common Core Bacterial Biomarkers of Bladder Cancer Based on Multiple Datasets.

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