Chemokine and chemokine receptor expression in kidney tumors: Molecular profiling of histological subtypes and association with metastasis

Jeffrey C. Gahan, Miguel Gosalbez, Travis Yates, Ezekiel E. Young, Diogo O. Escudero, Andrew Chi, Michael Garcia-Roig, Ramgopal Satyanarayana, Mark S. Soloway, Vincent G. Bird, Vinata B. Lokeshwar

Research output: Contribution to journalArticle

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Abstract

Purpose: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. Materials and Methods: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. Results: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers. Conclusions: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.

Original languageEnglish
Pages (from-to)827-833
Number of pages7
JournalJournal of Urology
Volume187
Issue number3
DOIs
StatePublished - Mar 1 2012

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Chemokine Receptors
Chemokines
Renal Cell Carcinoma
Oxyphilic Adenoma
Neoplasm Metastasis
Interleukin-8
Kidney
Interleukin-7
Neoplasms
Protein Isoforms
Interleukin-8 Receptors
Multivariate Analysis
Ligands
Inflammation
Polymerase Chain Reaction
Messenger RNA

Keywords

  • carcinoma
  • chemokines
  • kidney
  • neoplasm metastasis
  • prognosis
  • renal call

ASJC Scopus subject areas

  • Urology

Cite this

Chemokine and chemokine receptor expression in kidney tumors : Molecular profiling of histological subtypes and association with metastasis. / Gahan, Jeffrey C.; Gosalbez, Miguel; Yates, Travis; Young, Ezekiel E.; Escudero, Diogo O.; Chi, Andrew; Garcia-Roig, Michael; Satyanarayana, Ramgopal; Soloway, Mark S.; Bird, Vincent G.; Lokeshwar, Vinata B.

In: Journal of Urology, Vol. 187, No. 3, 01.03.2012, p. 827-833.

Research output: Contribution to journalArticle

Gahan, JC, Gosalbez, M, Yates, T, Young, EE, Escudero, DO, Chi, A, Garcia-Roig, M, Satyanarayana, R, Soloway, MS, Bird, VG & Lokeshwar, VB 2012, 'Chemokine and chemokine receptor expression in kidney tumors: Molecular profiling of histological subtypes and association with metastasis', Journal of Urology, vol. 187, no. 3, pp. 827-833. https://doi.org/10.1016/j.juro.2011.10.150
Gahan, Jeffrey C. ; Gosalbez, Miguel ; Yates, Travis ; Young, Ezekiel E. ; Escudero, Diogo O. ; Chi, Andrew ; Garcia-Roig, Michael ; Satyanarayana, Ramgopal ; Soloway, Mark S. ; Bird, Vincent G. ; Lokeshwar, Vinata B. / Chemokine and chemokine receptor expression in kidney tumors : Molecular profiling of histological subtypes and association with metastasis. In: Journal of Urology. 2012 ; Vol. 187, No. 3. pp. 827-833.
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abstract = "Purpose: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. Materials and Methods: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. Results: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71{\%} to 81{\%}) and specificity (75{\%} to 80{\%}) of all individual or combined markers. Conclusions: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80{\%} accuracy for predicting renal cell carcinoma metastasis.",
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T1 - Chemokine and chemokine receptor expression in kidney tumors

T2 - Molecular profiling of histological subtypes and association with metastasis

AU - Gahan, Jeffrey C.

AU - Gosalbez, Miguel

AU - Yates, Travis

AU - Young, Ezekiel E.

AU - Escudero, Diogo O.

AU - Chi, Andrew

AU - Garcia-Roig, Michael

AU - Satyanarayana, Ramgopal

AU - Soloway, Mark S.

AU - Bird, Vincent G.

AU - Lokeshwar, Vinata B.

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Purpose: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. Materials and Methods: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. Results: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers. Conclusions: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.

AB - Purpose: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. Materials and Methods: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. Results: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers. Conclusions: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.

KW - carcinoma

KW - chemokines

KW - kidney

KW - neoplasm metastasis

KW - prognosis

KW - renal call

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