Cited by 47MicroRNA in disease regulationBladder and Urothelial Cancer TreatmentsCancer-related molecular mechanisms research

A Panel of MicroRNA Signature as a Tool for Predicting Survival of Patients with Urothelial Carcinoma of the Bladder

Open access
Inamoto, Teruo, Uehara, Hirofumi, Akao, Yukihiro, Ibuki, Naokazu, Komura, Kazumasa, Takahara, Kiyoshi, Takai, Tomoaki, Uchimoto, Taizo +9 more·2018·Disease Markers

Abstract

Introduction and Objectives. MicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRNAs have been shown to modulate multiple signaling pathways that contribute to BC. To identify a panel of miRNA signature that can predict aggressive phenotype from normal nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB. Methods. To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UCB, miRNA expression was profiled in patients’ samples with an aggressive phenotype or nonaggressive phenotype using 3D-Gene miRNA labeling kit (Toray, Japan). To create a prognostic index model, we used the panel of 9-miRNA signature based on Cancer Genome Atlas (TCGA) data portal (TCGA Data Portal (https://tcgadata.nci.nih.gov/tcga/tcgaHome2.jsp)). miRNA expression data and corresponding clinical data, including outcome and staging information of 84 UCB patients, were obtained. The Kaplan-Meier and log-rank test were performed to quantify the survival functions in two groups. Results. Deregulation of nine miRNAs (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, and hsa-miR-33b-3p) was determined in UCB patients with aggressive phenotype compared with nonaggressive subject. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA UCB patients were ranked according to the prognostic score values. Of nine miRNAs, six were associated with high risk (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-4324, hsa-miR-34b-5p, and hsa-miR-135a-3p) and three were shown to be protective (hsa-miR-145-5p, hsa-miR-29c-3p, and hsa-miR-33b-3p). Patients with the high-risk miRNA signature exhibited poorer OS than patients expressing the low-risk miRNA profile (HR = 7.05, p<0.001). Conclusions. The miRNA array identified nine dysregulated miRNAs from clinical samples. This panel of nine-miRNA signature provides predictive and prognostic value of patients with UCB.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2018/5468672

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • miR-33b-3p functions as a tumor suppressor in some types of cancers.

    “miR-33b-3p also functions as tumor suppressor in some type of cancers (21, 22).”

    From miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer (2021) · cites this paper as [22]

    The Results section (page not provided) includes miR-33b-3p among nine miRNAs previously reported to have oncogenic or antioncogenic roles. It does not identify which role belongs to miR-33b-3p or show that it functions as a tumor suppressor in any cancer type; it also reports no significant individual association for miR-33b in the bladder-cancer analysis. (LLM, conf=0.77)

    Experimental — accuracy not yet measured
  • Downregulation of miR-33b-3p was found associated with aggressive phenotype of bladder cancer.

    “On the other hand, downregulation of miR-33b-3p was found associated with aggressive phenotype of bladder cancer (22).”

    From miR-33b-3p Acts as a Tumor Suppressor by Targeting DOCK4 in Prostate Cancer (2021) · cites this paper as [22]

    The Abstract Results report that miR-33b-3p was deregulated in aggressive versus nonaggressive bladder cancer and classify it as protective in the nine-miRNA signature. They do not specify that it was downregulated in aggressive tumors. The main Results section also says miR-33b had no significant individual association with the high-risk feature (page not given in our copy). (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 33

  1. [1]Lavery H. J. Stensland K. D. Niegisch G. Albers P. Droller M. J. Pathological T0 following radical cystectomy with or without neoadjuvant chemotherapy: a useful surrogate The Journal of Urology 2014 191 4 898 906 10.1016/j.juro.2013.10.142 2-s2.0-84898427546 24300483 · DOI
  2. [2]Santulli G. Exploiting microRNA specificity and selectivity: paving a sustainable path towards precision medicine Advances in Experimental Medicine and Biology 2015 888 1 3 10.1007/978-3-319-22671-2_1 2-s2.0-84949802062 26663175 PMC4871240 · DOI
  3. [3]Konishi H. Ichikawa D. Arita T. Otsuji E. Microarray technology and its applications for detecting plasma microRNA biomarkers in digestive tract cancers Methods in Molecular Biology 2016 1368 99 109 10.1007/978-1-4939-3136-1_8 2-s2.0-84965055053 26614071 · DOI
  4. [4]Kojima M. Sudo H. Kawauchi J. MicroRNA markers for the diagnosis of pancreatic and biliary-tract cancers PLoS One 2015 10 2, article e0118220 10.1371/journal.pone.0118220 2-s2.0-84923297763 25706130 PMC4338196 · DOI
  5. [5]Hisaoka M. Matsuyama A. Nagao Y. Identification of altered microRNA expression patterns in synovial sarcoma Genes, Chromosomes & Cancer 2011 50 3 137 145 10.1002/gcc.20837 2-s2.0-78650958694 21213367 · DOI
  6. [6]Cerdá-Olmedo G. Mena-Durán A. V. Monsalve V. Oltra E. Identification of a microRNA signature for the diagnosis of fibromyalgia PLoS One 2015 10 3, article e0121903 10.1371/journal.pone.0121903 2-s2.0-84925863961 25803872 PMC4372601 · DOI
  7. [7]Rikke B. A. Wynes M. W. Rozeboom L. M. Barón A. E. Hirsch F. R. Independent validation test of the vote-counting strategy used to rank biomarkers from published studies Biomarkers in Medicine 2015 9 8 751 761 10.2217/BMM.15.39 2-s2.0-84939797076 26223535 PMC4770796 · DOI
  8. [8]Ma M. Z. Kong X. Weng M. Z. Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis, experimental validation and clinical significance Journal of Experimental & Clinical Cancer Research 2013 32 1 p. 71 10.1186/1756-9966-32-71 2-s2.0-84884660965 24289824 PMC4176285 · DOI
  9. [9]Aguirre-Gamboa R. Trevino V. SurvMicro: assessment of miRNA-based prognostic signatures for cancer clinical outcomes by multivariate survival analysis Bioinformatics 2014 30 11 1630 1632 10.1093/bioinformatics/btu087 2-s2.0-84901341323 24519378 · DOI
  10. [10]Zhu Y. Davis S. Stephens R. Meltzer P. S. Chen Y. GEOmetadb: powerful alternative search engine for the Gene Expression Omnibus Bioinformatics 2008 24 23 2798 2800 10.1093/bioinformatics/btn520 2-s2.0-56649093037 18842599 PMC2639278 · DOI
  11. [11]Mattick J. S. Non-coding RNAs: the architects of eukaryotic complexity EMBO Reports 2001 2 11 986 991 10.1093/embo-reports/kve230 2-s2.0-0035195942 11713189 PMC1084129 · DOI
  12. [12]Liu G. Mattick J. S. Taft R. J. A meta-analysis of the genomic and transcriptomic composition of complex life Cell Cycle 2013 12 13 2061 2072 10.4161/cc.25134 2-s2.0-84879758121 23759593 PMC3737309 · DOI
  13. [13]Jarroux J. Morillon A. Pinskaya M. History, discovery, and classification of lncRNAs Advances in Experimental Medicine and Biology 2017 1008 1 46 10.1007/978-981-10-5203-3_1 2-s2.0-85027870729 28815535 · DOI
  14. [14]Jamali Z. Asl Aminabadi N. Attaran R. Pournagiazar F. Ghertasi Oskouei S. Ahmadpour F. MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: a systematic review and meta-analysis Oral Oncology 2015 51 4 321 331 10.1016/j.oraloncology.2015.01.008 2-s2.0-84933675265 25677760 · DOI
  15. [15]Boesch-Saadatmandi C. Wagner A. E. Wolffram S. Rimbach G. Effect of quercetin on inflammatory gene expression in mice liver in vivo – role of redox factor 1, miRNA-122 and miRNA-125b Pharmacological Research 2012 65 5 523 530 10.1016/j.phrs.2012.02.007 2-s2.0-84859801133 22402395 · DOI
  16. [16]Inamoto T. Taniguchi K. Takahara K. Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft Oncotarget 2015 6 25 21628 21635 10.18632/oncotarget.4129 2-s2.0-84940750339 26036261 PMC4673291 · DOI
  17. [17]Sand M. Skrygan M. Sand D. Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi Cell and Tissue Research 2013 351 1 85 98 10.1007/s00441-012-1514-5 2-s2.0-84872353504 23111773 · DOI
  18. [18]Imani S. Zhang X. Hosseinifard H. Fu S. Fu J. The diagnostic role of microRNA-34a in breast cancer: a systematic review and meta-analysis Oncotarget 2017 8 14 23177 23187 10.18632/oncotarget.15520 2-s2.0-85017027053 28423566 PMC5410295 · DOI
  19. [19]Marzi M. J. Puggioni E. M. R. Dall'Olio V. Differentiation-associated microRNAs antagonize the Rb-E2F pathway to restrict proliferation The Journal of Cell Biology 2012 199 1 77 95 10.1083/jcb.201206033 2-s2.0-84869135392 23027903 PMC3461518 · DOI
  20. [20]Darnet S. Moreira F. C. Hamoy I. G. High-throughput sequencing of miRNAs reveals a tissue signature in gastric cancer and suggests novel potential biomarkers Bioinformatics and Biology Insights 2015 9s1 10.4137/BBI.S23773 2-s2.0-84939636421 26157332 PMC4485834 · DOI
  21. [21]Wu Q. Liu X. Yan H. B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells BMC Cancer 2014 14 1 p. 418 10.1186/1471-2407-14-418 2-s2.0-84904746390 24917186 PMC4065600 · DOI
  22. [22]Takai T. Yoshikawa Y. Inamoto T. A novel combination RNAi toward Warburg effect by replacement with miR-145 and silencing of PTBP1 induces apoptotic cell death in bladder cancer cells International Journal of Molecular Sciences 2017 18 1 10.3390/ijms18010179 2-s2.0-85009875957 28106737 PMC5297811 · DOI
  23. [23]Minami K. Taniguchi K. Sugito N. MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells Oncotarget 2017 8 20 33064 33077 10.18632/oncotarget.16524 2-s2.0-85019264789 28380435 PMC5464850 · DOI
  24. [24]Wu D. Huang P. Wang L. Zhou Y. Pan H. Qu P. MicroRNA-143 inhibits cell migration and invasion by targeting matrix metalloproteinase 13 in prostate cancer Molecular Medicine Reports 2013 8 2 626 630 10.3892/mmr.2013.1501 2-s2.0-84879957962 23732700 · DOI
  25. [25]Wu D. Li M. Wang L. microRNA145 inhibits cell proliferation, migration and invasion by targeting matrix metallopeptidase-11 in renal cell carcinoma Molecular Medicine Reports 2014 10 1 393 398 10.3892/mmr.2014.2149 2-s2.0-84901469282 24737449 · DOI
  26. [26]Zhang Q. H. Sun H. M. Zheng R. Z. Meta-analysis of microRNA-183 family expression in human cancer studies comparing cancer tissues with noncancerous tissues Gene 2013 527 1 26 32 10.1016/j.gene.2013.06.006 2-s2.0-84881224445 23791657 · DOI
  27. [27]Wang J. Zhao J. Shi M. Elevated expression of miR-210 predicts poor survival of cancer patients: a systematic review and meta-analysis PLoS One 2014 9 2, article e89223 10.1371/journal.pone.0089223 2-s2.0-84895890496 24586608 PMC3930667 · DOI
  28. [28]Hautmann R. E. de Petriconi R. C. Pfeiffer C. Volkmer B. G. Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients European Urology 2012 61 5 1039 1047 10.1016/j.eururo.2012.02.028 2-s2.0-84859435388 22381169 · DOI
  29. [29]Lorentzen E. Conti E. Structural basis of 3′ end RNA recognition and exoribonucleolytic cleavage by an exosome RNase PH core Molecular Cell 2005 20 3 473 481 10.1016/j.molcel.2005.10.020 2-s2.0-27644496002 16285928 · DOI
  30. [30]Guancial E. A. Bellmunt J. Yeh S. Rosenberg J. E. Berman D. M. The evolving understanding of microRNA in bladder cancer Urologic Oncology 2014 32 1 41.e31 41.e40 10.1016/j.urolonc.2013.04.014 2-s2.0-84890788122 23911686 PMC4502576 · DOI
  31. [31]Guancial E. A. Werner L. Bellmunt J. FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder Cancer Medicine 2014 3 4 835 844 10.1002/cam4.262 2-s2.0-84924416523 24846059 PMC4303151 · DOI
  32. [32]Palmbos P. L. Wang L. Yang H. ATDC/TRIM29 drives invasive bladder cancer formation through miRNA-mediated and epigenetic mechanisms Cancer Research 2015 75 23 5155 5166 10.1158/0008-5472.CAN-15-0603 2-s2.0-84955282032 26471361 PMC4668224 · DOI
  33. [33]Regazzo G. Terrenato I. Spagnuolo M. A restricted signature of serum miRNAs distinguishes glioblastoma from lower grade gliomas Journal of Experimental & Clinical Cancer Research 2016 35 1 p. 124 10.1186/s13046-016-0393-0 2-s2.0-84982806385 27476114 PMC4967504 · DOI

Cited by

Sorted by citations

Authors
Inamoto, T., Uehara, H., Akao, Y., Ibuki, N., Komura, K., Takahara, K., Takai, T., Uchimoto, T., Saito, K., Tanda, N., Yoshikawa, Y., Minami, K., Hirano, H., Nomi, H., Kato, R., Hayashi, T., & Azuma, H.
Affiliations
  • Osaka Medical and Pharmaceutical University (JP)
  • Gifu University (JP)
  • Osaka University of Pharmaceutical Sciences (JP)
Corresponding author
Inamoto, Teruo
Venue
Disease Markers
Publisher
Wiley
Published
2018-06-20
Volume
2018
Pages
1-6
ISSN
  • 0278-0240 (ISSN-L)
  • 1875-8630
OpenAlex
W2809331138
Cited by
47
References
0
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 8
FWCI
2.04
Type
journal article
Language
en
Open access
Locations
  • Disease Markers (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Japan Society for the Promotion of Science (17K16821, 15K10611)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
bladder urothelial carcinoma, microRNA signature, prognostic factors, survival prediction, tumor aggressiveness, miR-99a-5p, miR-100-5p, miR-125b-5p, miR-145, miR-34b-5p, miR-29c-3p, prognostic score
MeSH terms
Aged, Aged, 80 and over, Urinary Bladder Neoplasms, Carcinoma, Humans, Male, Biomarkers, Tumor, Survival Analysis, Urothelium, MicroRNAs, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review