Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis

Mario W. Kramer, Diogo O. Escudero, Soum D. Lokeshwar, Roozbeh Golshani, Obi O. Ekwenna, Kristell Acosta, Axel S. Merseburger, Mark Soloway, Vinata B Lokeshwar

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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, CD44s 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.

Original languageEnglish (US)
Pages (from-to)1197-1209
Number of pages13
JournalCancer
Volume117
Issue number6
DOIs
StatePublished - Mar 15 2011

Fingerprint

Hyaluronic Acid
Urinary Bladder Neoplasms
Neoplasms
Neoplasm Metastasis
Recurrence
Hyaluronoglucosaminidase
Tumor Biomarkers
Urinary Bladder
Multivariate Analysis
Biomarkers
Lymph Nodes
Immunohistochemistry
Urine
Staining and Labeling
Polymerase Chain Reaction
Survival
Mortality

Keywords

  • HA receptors
  • HA synthase
  • HYAL-1
  • diagnosis
  • hyaluronic acid
  • hyaluronidase
  • prognostic makers
  • recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kramer, M. W., Escudero, D. O., Lokeshwar, S. D., Golshani, R., Ekwenna, O. O., Acosta, K., ... Lokeshwar, V. B. (2011). Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis. Cancer, 117(6), 1197-1209. https://doi.org/10.1002/cncr.25565

Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis. / Kramer, Mario W.; Escudero, Diogo O.; Lokeshwar, Soum D.; Golshani, Roozbeh; Ekwenna, Obi O.; Acosta, Kristell; Merseburger, Axel S.; Soloway, Mark; Lokeshwar, Vinata B.

In: Cancer, Vol. 117, No. 6, 15.03.2011, p. 1197-1209.

Research output: Contribution to journalArticle

Kramer, MW, Escudero, DO, Lokeshwar, SD, Golshani, R, Ekwenna, OO, Acosta, K, Merseburger, AS, Soloway, M & Lokeshwar, VB 2011, 'Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis', Cancer, vol. 117, no. 6, pp. 1197-1209. https://doi.org/10.1002/cncr.25565
Kramer MW, Escudero DO, Lokeshwar SD, Golshani R, Ekwenna OO, Acosta K et al. Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis. Cancer. 2011 Mar 15;117(6):1197-1209. https://doi.org/10.1002/cncr.25565
Kramer, Mario W. ; Escudero, Diogo O. ; Lokeshwar, Soum D. ; Golshani, Roozbeh ; Ekwenna, Obi O. ; Acosta, Kristell ; Merseburger, Axel S. ; Soloway, Mark ; Lokeshwar, Vinata B. / Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis. In: Cancer. 2011 ; Vol. 117, No. 6. pp. 1197-1209.
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abstract = "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, CD44s 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.",
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T1 - Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis

AU - Kramer, Mario W.

AU - Escudero, Diogo O.

AU - Lokeshwar, Soum D.

AU - Golshani, Roozbeh

AU - Ekwenna, Obi O.

AU - Acosta, Kristell

AU - Merseburger, Axel S.

AU - Soloway, Mark

AU - Lokeshwar, Vinata B

PY - 2011/3/15

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N2 - 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, CD44s 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.

AB - 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, CD44s 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.

KW - HA receptors

KW - HA synthase

KW - HYAL-1

KW - diagnosis

KW - hyaluronic acid

KW - hyaluronidase

KW - prognostic makers

KW - recurrence

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