期刊
CANCER
卷 117, 期 6, 页码 1197-1209出版社
WILEY
DOI: 10.1002/cncr.25565
关键词
prognostic makers; hyaluronic acid; HA synthase; HYAL-1; HA receptors; hyaluronidase; diagnosis; recurrence
类别
资金
- National Institutes of Health [2R01CA072821-11, R01 CA 123063-03, R01 CA 123063-04]
- Florida Department of Health-James and Esther King Biomedical Research Program [10KT-01]
- CURED Department of Urology
- Woman's Cancer Association of the University of Miami
- International Academy of Life Sciences, Biomedical Science Exchange Program
BACKGROUND: Cancer biomarkers are the backbone for the implementation of individualized approaches to bladder cancer (BCa). Hyaluronic acid (HA) and all 7 members of the HA family, that is, HA synthases (HA1, HA2, HA3), HYAL-1 hyaluronidase, and HA receptors (CD44s, CD44v, and RHAMM), function in tumor growth and progression. However, the diagnostic and prognostic potential of these 7 HA family members has not been compared simultaneously in any cancer. We evaluated the diagnostic and prognostic potential of HA family members in BCa. METHODS: Using quantitative PCR and immunohistochemistry, expression of HA family members was evaluated in prospectively collected bladder tissues (n = 72); mean and median follow-up were 29.6 +/- 5.3 and 24 months, respectively. Transcript levels were also measured in exfoliated urothelial cells from urine specimens (n = 148). RESULTS: Among the HA family members, transcript levels of the HA synthases, HYAL-1, CD44v, and RHAMM were 4- to 16-fold higher in BCa tissues than in normal tissues (P < .0001); however, CD445 levels were lower. In univariate and multivariate analyses, tumor stage (P = .003), lymph node invasion (P = .033), HYAL-1 (P = .019), and HAS1 (P = .027) transcript levels, and HYAL-1 staining (P = .021) were independently associated with metastasis. Tumor stage (P = .019) and HYAL-1 (P = .046) transcript levels were also associated with disease-specific mortality. Although HA synthase and HYAL-1 transcript levels were elevated in exfoliated urothelial cells from BCa patients, the combined HAS2-HYAL-1 expression detected BCa with an overall sensitivity of 85.4% and a specificity of 79.5% and predicted BCa recurrence within 6 months (P = .004; RR = 6.7). CONCLUSIONS: HYAL-1 and HAS1 expression predicted BCa metastasis, and HYAL-1 expression also predicted disease-specific survival. Furthermore, the combined HAS2-HYAL-1 biomarker detected BCa and significantly predicted its recurrence. Cancer 2011;117:1197-209. (C) 2070 American Cancer Society.
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