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Tumor Biology

, Volume 35, Issue 11, pp 11435–11442 | Cite as

Appraisal of diagnostic ability of UCA1 as a biomarker of carcinoma of the urinary bladder

  • A. K. Srivastava
  • P. K. Singh
  • S. K. Rath
  • D. Dalela
  • M. M. Goel
  • M. L. B. Bhatt
Research Article

Abstract

Initial diagnosis of carcinoma of the urinary bladder remains to be a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Urothelial cancer associated 1 (UCA1) is a novel non-coding RNA gene, which plays a pivotal role in bladder cancer progression. Our aim is to investigate the significance of urinary UCA1 for the non-invasive diagnosis of transitional cell carcinoma (TCC) of the urinary bladder. We examined UCA1 expression in a bladder cancer cell line (T24) and in urine of 28 healthy individuals, 46 patients of non-malignant disorders, and 117 cases (69 primary and 48 recurrent cases) of histologically proven TCC prior to transurethral resection by using real-time PCR and compared it with voided urinary cytology. UCA1 expression was found in T24 cell line and also found to be significantly higher in the cancer group as compared to the controls (p < 0.001). UCA1 messenger RNA (mRNA) expression showed a significant (p < 0.05) association with stage and grade (p < 0.05). UCA1 showed a sensitivity of 79.49 % and a specificity of 79.73 % (p < 0.001), whereas urine cytology had a sensitivity of 66.67 % and a specificity of 95.95 % for TCC cases. Higher expression of UCA1 was associated with high grade (G2–G3, sensitivity = 84.09 %) (p < 0.001). UCA1 mRNA expression did not significantly correlate with the patient’s age, sex, and smoking habit (p > 0.05). UCA1 can be used as a non-invasive diagnostic biomarker for TCC bladder as an adjunct to cytology in the early diagnosis of primary urinary bladder cancer.

Keywords

UCA1 Biomarker Carcinoma of the urinary bladder Voided urine cytology Noninvasive diagnosis Urinary marker 

Notes

Acknowledgments

All authors are also thankful to Dr. Seema Nayak and Dr. S. P. Mishra for their invaluable contribution. We thank all the subjects for their participation in the study. The first author (Anupam Kumar Srivastava) is thankful to the Indian Council of Medial Research, New Delhi, India, for awarding Senior Research Fellowship (SRF IRIS ID: 2010-03160) under the guidance of the corresponding author.

Conflicts of interest

None

References

  1. 1.
    Agarwal PK, Black PC, Kamat AM. Considerations on the use of diagnostic markers in management of patients with bladder cancer. World J Urol. 2008;26:39–4.PubMedCrossRefGoogle Scholar
  2. 2.
    Grossfeld GD, Carroll PR. Evaluation of asymptomatic microscopic haematuria. Urol Clin N Am. 1998;25:661–6.CrossRefGoogle Scholar
  3. 3.
    Boman H, Hedelin H, Jacobsson S, et al. Newly diagnosed bladder cancer: the relationship of initial symptoms, degree of microhematuria and tumor marker status. J Urol. 2002;168:1955–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Goebell PJ, Groshen SL, Schmitz-Drager BJ. Guidelines for development of diagnostic markers in bladder cancer. World J Urol. 2008;26:5–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Justin P, Philippe ES. Current and emerging bladder cancer urinary biomarkers. Sci World J. 2011;11:1103–12.CrossRefGoogle Scholar
  6. 6.
    Fan Wang X, Xiao L, Xiea J, et al. UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett. 2008;582:1919–27.PubMedCrossRefGoogle Scholar
  7. 7.
    Jern P, Sperber GO, Ahlsen G, et al. Sequence variability, gene structure, and expression of full-length human endogenous retrovirus H. J Virol. 2005;79:6325–7.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Chen Yang X, Li Y, Wang LZ, et al. Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells. Gene. 2012;496:8–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang XS, Zhang Z, Wang HC, et al. Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res. 2006;12(16):4851–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang Z, Hao H, Zhang CJ, et al. Evaluation of novel gene UCA1 as a tumour biomarker for the detection of bladder cancer. Zhonghua Yi Xue Za Zhi. 2012;92(6):384–7.PubMedGoogle Scholar
  11. 11.
    Sobin LH, Wittekind C. TNM classification of malignant tumours. 6th ed. New York: Wiley; 2002.Google Scholar
  12. 12.
    Mostofi FK, Sobin LH, Torloni H et al. Histological typing of urinary bladder tumours. World Health Organization Geneva. Volume 10, 1973.Google Scholar
  13. 13.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25:402–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Bewick V, Cheek L, Ball J. Statistics review 13: receiver operating characteristic curves. Crit Care. 2004;8:508–12.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Srivastava AK, Singh PK, Singh P, et al. Clinical experience with UCA1 as a biomarker for non-muscular invasive bladder cancer. Eur Urol Suppl. 2011;10(2):74.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • A. K. Srivastava
    • 1
  • P. K. Singh
    • 1
  • S. K. Rath
    • 2
  • D. Dalela
    • 3
  • M. M. Goel
    • 4
  • M. L. B. Bhatt
    • 5
  1. 1.Department of RadiotherapyKing George’s Medical UniversityLucknowIndia
  2. 2.Genotoxicity Laboratory, Division of ToxicologyCSIR-Central Drug Research InstituteLucknowIndia
  3. 3.Department of UrologyKing George’s Medical UniversityLucknowIndia
  4. 4.Department of PathologyKing George’s Medical UniversityLucknowIndia
  5. 5.Department of Radiation OncologyDr. Ram Manohar Lohia Institute of Medical SciencesLucknowIndia

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