nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

08.05.2017 | Original Article – Cancer Research

Urinary transcript quantitation of CK20 and IGF2 for the non-invasive bladder cancer detection

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Cytokeratin 20 (CK20) and insulin-like growth factor 2 (IGF2) were previously proposed to be elevated in clinical samples from patients with bladder cancer (BCa). A two cohort design validation study was used to assess the relevance for BCa detection by transcript quantitation of both markers in urine samples. Their diagnostic value was assessed in comparison with voided urine cytology (VUC).

Methods

RNA isolation was carried out using cellular sediments of urine samples from 196/103 histologically positive BCa patients, as well as 97/50 control subjects for the test (TC) and validation cohort (VC), respectively. Urinary transcript levels of CK20 and IGF2 were determined by qPCR.

Results

Relative transcript levels were significantly elevated 3.4/11-fold for CK20 and 188/64-fold for IGF2 (p < 0.001) in urine sediments of BCa patients compared to controls in the TC and VC, respectively. In a combined analysis, the resulting sensitivity (SN) (SN_TC: 77.9; SN_VC: 90.3%) and specificity (SP) (SP_TC: 88.0; SP_VC: 84.0%) were similar to that of VUC. The sensitivity of VUC in combination with CK20 and IGF2 was considerably increased (SN_TC: 94.6; SN_VC: 93.2%) while specificity was reduced (SP_TC: 72.0; SP_VC: 82.0%) compared to VUC alone in the test and validation cohort.

Conclusions

Transcript levels of IGF2 and CK20 enabled the detection of BCa with a diagnostic performance similar to VUC. Combined analysis of voided urine cytology together with altered transcript levels of CK20 and IGF2 enhanced sensitivity, but did not improve overall test performance.

Babjuk M, Böhle A, Burger M et al (2016) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 71:447–461. doi:10.1016/j.eururo.2016.05.041 CrossRefPubMed

Breyer J, Otto W, Erben P et al (2017) In stage pT1 non-muscle-invasive bladder cancer (NMIBC), high KRT20 and low KRT5 mRNA expression identify the luminal subtype and predict recurrence and survival. Virchows Arch 470:267–274. doi:10.1007/s00428-017-2064-8 CrossRefPubMed

Chau K, Rosen L, Coutsouvelis C et al (2015) Accuracy and risk of malignancy for diagnostic categories in urine cytology at a large tertiary institution: accuracy of urine cytology. Cancer Cytopathol 123:10–18. doi:10.1002/cncy.21477 CrossRefPubMed

Choi W, Porten S, Kim S et al (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25:152–165. doi:10.1016/j.ccr.2014.01.009 CrossRefPubMedPubMedCentral

Chou R, Gore JL, Buckley D et al (2015) Urinary biomarkers for diagnosis of bladder cancer: a systematic review and meta-analysis. Ann Intern Med 163:922–931. doi:10.7326/M15-0997 CrossRefPubMed

Christoph F, Weikert S, Wolff I et al (2007) Urinary cytokeratin 20 mRNA expression has the potential to predict recurrence in superficial transitional cell carcinoma of the bladder. Cancer Lett 245:121–126. doi:10.1016/j.canlet.2005.12.038 CrossRefPubMed

Dong Y, Li J, Han F et al (2015) High IGF2 expression is associated with poor clinical outcome in human ovarian cancer. Oncol Rep 34:936–942. doi:10.3892/or.2015.4048 PubMed

Eissa S, Zohny SF, Swellam M et al (2008) Comparison of CD44 and cytokeratin 20 mRNA in voided urine samples as diagnostic tools for bladder cancer. Clin Biochem 41:1335–1341. doi:10.1016/j.clinbiochem.2008.08.085 CrossRefPubMed

Eissa S, Swellam M, Amin A et al (2011) The clinical relevance of urine-based markers for diagnosis of bladder cancer. Med Oncol 28:513–518. doi:10.1007/s12032-010-9422-6 CrossRefPubMed

Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012: Globocan 2012. Int J Cancer 136:E359–E386. doi:10.1002/ijc.29210 CrossRefPubMed

Hedegaard J, Lamy P, Nordentoft I et al (2016) Comprehensive transcriptional analysis of early-stage urothelial carcinoma. Cancer Cell 30:27–42. doi:10.1016/j.ccell.2016.05.004 CrossRefPubMed

Humphrey PA, Moch H, Cubilla AL et al (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs—Part B: prostate and bladder tumours. Eur Urol 70:106–119. doi:10.1016/j.eururo.2016.02.028 CrossRefPubMed

Hurst CD, Knowles MA (2014) Molecular subtyping of invasive bladder cancer: time to divide and rule? Cancer Cell 25:135–136. doi:10.1016/j.ccr.2014.01.026 CrossRefPubMed

Jiang X, Du L, Wang L et al (2015) Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer: serum miRNA Signature for BC detection. Int J Cancer 136:854–862. doi:10.1002/ijc.29041 CrossRefPubMed

German Cancer Society, German Cancer Aid, AMWF (2016) German Guideline Program in Oncology (GGPO): S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinoms, Langversion 1.1, AWMF-Registrierungsnummer 03 2/038OL. http://leitlinienprogramm-onkologie.de/Harnblasenkarzinom.92.0.html

Livingstone C (2013) IGF2 and cancer. Endocr Relat Cancer 20:R321–R339. doi:10.1530/ERC-13-0231 CrossRefPubMed

McConkey DJ, Choi W, Shen Y et al (2016) A prognostic gene expression signature in the molecular classification of chemotherapy-naïve urothelial cancer is predictive of clinical outcomes from neoadjuvant chemotherapy: a Phase 2 Trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with Bevacizumab in urothelial cancer. Eur Urol 69:855–862. doi:10.1016/j.eururo.2015.08.034 CrossRefPubMed

Nandagopal L, Sonpavde G (2016) Circulating biomarkers in bladder cancer. Bladder Cancer 2:369–379. doi:10.3233/BLC-160075 CrossRefPubMedPubMedCentral

Papanicolaou GN, Marshall VF (1945) Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science 101:519–520. doi:10.1126/science.101.2629.519 CrossRefPubMed

Pu X-Y, Wang Z-P, Chen Y-R et al (2008) The value of combined use of survivin, cytokeratin 20 and mucin 7 mRNA for bladder cancer detection in voided urine. J Cancer Res Clin Oncol 134:659–665. doi:10.1007/s00432-007-0331-9 CrossRefPubMed

Ribal MJ, Mengual L, Lozano JJ et al (2016) Gene expression test for the non-invasive diagnosis of bladder cancer: a prospective, blinded, international and multicenter validation study. Eur J Cancer 54:131–138. doi:10.1016/j.ejca.2015.11.003 CrossRefPubMed

Schmidt J, Propping C, Siow W-Y et al (2016) Diagnostic and prognostic value of bladder cancer-related transcript markers in urine. J Cancer Res Clin Oncol 142:401–414. doi:10.1007/s00432-015-2037-8 CrossRefPubMed

Siracusano S, Niccolini B, Knez R et al (2005) The simultaneous use of telomerase, cytokeratin 20 and CD4 for bladder cancer detection in urine. Eur Urol 47:327–333. doi:10.1016/j.eururo.2004.10.007 CrossRefPubMed

Sobin LH, Gospodarowicz MK, Wittekind C (eds) (2011) TNM classification of malignant tumours. Wiley-Blackwell, Hoboken

Svatek RS, Hollenbeck BK, Holmäng S et al (2014) The economics of bladder cancer: costs and considerations of caring for this disease. Eur Urol 66:253–262. doi:10.1016/j.eururo.2014.01.006 CrossRefPubMed

Urquidi V, Netherton M, Gomes-Giacoia E et al (2016) Urinary mRNA biomarker panel for the detection of urothelial carcinoma. Oncotarget 7:38731–38740. doi:10.18632/oncotarget.9587 CrossRefPubMedPubMedCentral

van der Heijden AG, Mengual L, Lozano JJ et al (2016) A five-gene expression signature to predict progression in T1G3 bladder cancer. Eur J Cancer 64:127–136. doi:10.1016/j.ejca.2016.06.003 CrossRefPubMed

van Rhijn BWG, van der Poel HG, van der Kwast TH (2005) Urine markers for bladder cancer surveillance: a systematic review. Eur Urol 47:736–748. doi:10.1016/j.eururo.2005.03.014 CrossRefPubMed

Vennin C, Spruyt N, Robin Y-M et al (2017) The long non-coding RNA 91H increases aggressive phenotype of breast cancer cells and up-regulates H19/IGF2 expression through epigenetic modifications. Cancer Lett 385:198–206. doi:10.1016/j.canlet.2016.10.023 CrossRefPubMed

Vidal SJ, Rodriguez-Bravo V, Quinn SA et al (2015) A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer. Cancer Cell 27:223–239. doi:10.1016/j.ccell.2014.11.013 CrossRefPubMedPubMedCentral

Weischenfeldt J, Dubash T, Drainas AP et al (2017) Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking. Nat Genet 49:65–74. doi:10.1038/ng.3722 CrossRefPubMed

Xylinas E, Kluth LA, Rieken M et al (2014) Urine markers for detection and surveillance of bladder cancer. Urol Oncol 32:222–229. doi:10.1016/j.urolonc.2013.06.001 CrossRefPubMed

Yafi FA, Brimo F, Auger M et al (2014) Is the performance of urinary cytology as high as reported historically? A contemporary analysis in the detection and surveillance of bladder cancer. Urol Oncol 32:27e1–27e6. doi:10.1016/j.urolonc.2012.09.011 CrossRef

Ye F, Wang L, Castillo-Martin M et al (2014) Featured review article biomarkers for bladder cancer management: present and future. Am J Clin Exp Urol 2:1–14CrossRefPubMedPubMedCentral

Titel: Urinary transcript quantitation of CK20 and IGF2 for the non-invasive bladder cancer detection
Publikationsdatum: 08.05.2017
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2017
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2433-3

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Urinary transcript quantitation of CK20 and IGF2 for the non-invasive bladder cancer detection

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2017

ZCCHC12, a novel oncogene in papillary thyroid cancer

Conversion of hormone and HER-2 receptor in metachronous neck metastases from breast carcinoma

Development of a novel prognostic signature of long non-coding RNAs in lung adenocarcinoma

Impact of intra-tumoral IL17A and IL32 gene expression on T-cell responses and lymph node status in breast cancer patients

Erratum to: Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor cell clusters and macrometastases: displaying heterogeneity and crater-like structure on inner layer

Personalized axillary dissection: the number of excised lymph nodes of nodal-positive breast cancer patients has no significant impact on relapse-free and overall survival

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie