Elevated plasma tissue inhibitor of metalloproteinase-1 levels predict decreased survival in castration-resistant prostate cancer patients

William K. Oh, Roberto Vargas, Susanna Jacobus, Kim Leitzel, Meredith M. Regan, Peter Hamer, Karen Pierce, Sheryl Brown-Shimer, Walter Carney, Suhail M. Ali, Philip W. Kantoff, Allan Lipton

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has paradoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of matrix metalloproteinases and apoptosis as well as promotion of angiogenesis and tumor growth. Elevated TIMP-1 levels have been associated with a poorer prognosis in multiple cancers. Methods: Ethylenediaminetetraacetic acid plasma TIMP-1 was determined in 362 castration-resistant prostate cancer (PC) patients using a TIMP-1 enzyme-linked immunosorbent assay. All patients with castration-resistant PC and available plasma were identified from an institutional database. Overall survival was analyzed using the Kaplan-Meier method and Cox modeling on plasma TIMP-1 tertiles. Results: Patients were evaluated in pilot (n = 60) and primary (n = 302) sets. Median follow-up from diagnosis was 5.8 and 6.6 years, respectively. Median plasma TIMP-1 levels were 335 and 183 ng/mL in the pilot and primary sets, respectively. Overall survival was significantly shorter with each higher tertile of TIMP-1 in both datasets (P<.001). For the primary cohort, hazard ratio of (HR) death and median survival by plasma TIMP-1 tertile levels were: low, HR 1.0, 43 months; middle, HR 1.7, 27 months; high, HR 2.4, 19 months. In the primary set, significant covariates in the adjusted Cox regression model were: TIMP-1 level (mid or high vs low tertile), prostate-specific antigen (>20 vs ≤ 20 ng/mL), alkaline phosphatase (>102 vs â102 U/L), Eastern Cooperative Oncology Group performance status (1 + vs 0), and Gleason score (7 or 8 vs ≤ 6). Conclusions: Elevated plasma TIMP-1 levels predicted decreased survival in metastatic castration-resistant PC patients, independent of known prognostic markers.

Original languageEnglish (US)
Pages (from-to)517-525
Number of pages9
JournalCancer
Volume117
Issue number3
DOIs
StatePublished - Feb 1 2011

Fingerprint

Tissue Inhibitor of Metalloproteinase-1
Castration
Prostatic Neoplasms
Survival
Neoplasm Grading
Matrix Metalloproteinases
Edetic Acid
Alkaline Phosphatase
Neoplasms
Carcinogenesis
Enzyme-Linked Immunosorbent Assay
Databases
Apoptosis
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Oh, William K. ; Vargas, Roberto ; Jacobus, Susanna ; Leitzel, Kim ; Regan, Meredith M. ; Hamer, Peter ; Pierce, Karen ; Brown-Shimer, Sheryl ; Carney, Walter ; Ali, Suhail M. ; Kantoff, Philip W. ; Lipton, Allan. / Elevated plasma tissue inhibitor of metalloproteinase-1 levels predict decreased survival in castration-resistant prostate cancer patients. In: Cancer. 2011 ; Vol. 117, No. 3. pp. 517-525.
@article{f48bef6d7a9946beb33cc34d892038d4,
title = "Elevated plasma tissue inhibitor of metalloproteinase-1 levels predict decreased survival in castration-resistant prostate cancer patients",
abstract = "Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has paradoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of matrix metalloproteinases and apoptosis as well as promotion of angiogenesis and tumor growth. Elevated TIMP-1 levels have been associated with a poorer prognosis in multiple cancers. Methods: Ethylenediaminetetraacetic acid plasma TIMP-1 was determined in 362 castration-resistant prostate cancer (PC) patients using a TIMP-1 enzyme-linked immunosorbent assay. All patients with castration-resistant PC and available plasma were identified from an institutional database. Overall survival was analyzed using the Kaplan-Meier method and Cox modeling on plasma TIMP-1 tertiles. Results: Patients were evaluated in pilot (n = 60) and primary (n = 302) sets. Median follow-up from diagnosis was 5.8 and 6.6 years, respectively. Median plasma TIMP-1 levels were 335 and 183 ng/mL in the pilot and primary sets, respectively. Overall survival was significantly shorter with each higher tertile of TIMP-1 in both datasets (P<.001). For the primary cohort, hazard ratio of (HR) death and median survival by plasma TIMP-1 tertile levels were: low, HR 1.0, 43 months; middle, HR 1.7, 27 months; high, HR 2.4, 19 months. In the primary set, significant covariates in the adjusted Cox regression model were: TIMP-1 level (mid or high vs low tertile), prostate-specific antigen (>20 vs ≤ 20 ng/mL), alkaline phosphatase (>102 vs {\^a}102 U/L), Eastern Cooperative Oncology Group performance status (1 + vs 0), and Gleason score (7 or 8 vs ≤ 6). Conclusions: Elevated plasma TIMP-1 levels predicted decreased survival in metastatic castration-resistant PC patients, independent of known prognostic markers.",
author = "Oh, {William K.} and Roberto Vargas and Susanna Jacobus and Kim Leitzel and Regan, {Meredith M.} and Peter Hamer and Karen Pierce and Sheryl Brown-Shimer and Walter Carney and Ali, {Suhail M.} and Kantoff, {Philip W.} and Allan Lipton",
year = "2011",
month = "2",
day = "1",
doi = "10.1002/cncr.25394",
language = "English (US)",
volume = "117",
pages = "517--525",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

Oh, WK, Vargas, R, Jacobus, S, Leitzel, K, Regan, MM, Hamer, P, Pierce, K, Brown-Shimer, S, Carney, W, Ali, SM, Kantoff, PW & Lipton, A 2011, 'Elevated plasma tissue inhibitor of metalloproteinase-1 levels predict decreased survival in castration-resistant prostate cancer patients', Cancer, vol. 117, no. 3, pp. 517-525. https://doi.org/10.1002/cncr.25394

Elevated plasma tissue inhibitor of metalloproteinase-1 levels predict decreased survival in castration-resistant prostate cancer patients. / Oh, William K.; Vargas, Roberto; Jacobus, Susanna; Leitzel, Kim; Regan, Meredith M.; Hamer, Peter; Pierce, Karen; Brown-Shimer, Sheryl; Carney, Walter; Ali, Suhail M.; Kantoff, Philip W.; Lipton, Allan.

In: Cancer, Vol. 117, No. 3, 01.02.2011, p. 517-525.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Elevated plasma tissue inhibitor of metalloproteinase-1 levels predict decreased survival in castration-resistant prostate cancer patients

AU - Oh, William K.

AU - Vargas, Roberto

AU - Jacobus, Susanna

AU - Leitzel, Kim

AU - Regan, Meredith M.

AU - Hamer, Peter

AU - Pierce, Karen

AU - Brown-Shimer, Sheryl

AU - Carney, Walter

AU - Ali, Suhail M.

AU - Kantoff, Philip W.

AU - Lipton, Allan

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has paradoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of matrix metalloproteinases and apoptosis as well as promotion of angiogenesis and tumor growth. Elevated TIMP-1 levels have been associated with a poorer prognosis in multiple cancers. Methods: Ethylenediaminetetraacetic acid plasma TIMP-1 was determined in 362 castration-resistant prostate cancer (PC) patients using a TIMP-1 enzyme-linked immunosorbent assay. All patients with castration-resistant PC and available plasma were identified from an institutional database. Overall survival was analyzed using the Kaplan-Meier method and Cox modeling on plasma TIMP-1 tertiles. Results: Patients were evaluated in pilot (n = 60) and primary (n = 302) sets. Median follow-up from diagnosis was 5.8 and 6.6 years, respectively. Median plasma TIMP-1 levels were 335 and 183 ng/mL in the pilot and primary sets, respectively. Overall survival was significantly shorter with each higher tertile of TIMP-1 in both datasets (P<.001). For the primary cohort, hazard ratio of (HR) death and median survival by plasma TIMP-1 tertile levels were: low, HR 1.0, 43 months; middle, HR 1.7, 27 months; high, HR 2.4, 19 months. In the primary set, significant covariates in the adjusted Cox regression model were: TIMP-1 level (mid or high vs low tertile), prostate-specific antigen (>20 vs ≤ 20 ng/mL), alkaline phosphatase (>102 vs â102 U/L), Eastern Cooperative Oncology Group performance status (1 + vs 0), and Gleason score (7 or 8 vs ≤ 6). Conclusions: Elevated plasma TIMP-1 levels predicted decreased survival in metastatic castration-resistant PC patients, independent of known prognostic markers.

AB - Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has paradoxical multifunctional roles in tumorigenesis: inhibition of the catalytic activity of matrix metalloproteinases and apoptosis as well as promotion of angiogenesis and tumor growth. Elevated TIMP-1 levels have been associated with a poorer prognosis in multiple cancers. Methods: Ethylenediaminetetraacetic acid plasma TIMP-1 was determined in 362 castration-resistant prostate cancer (PC) patients using a TIMP-1 enzyme-linked immunosorbent assay. All patients with castration-resistant PC and available plasma were identified from an institutional database. Overall survival was analyzed using the Kaplan-Meier method and Cox modeling on plasma TIMP-1 tertiles. Results: Patients were evaluated in pilot (n = 60) and primary (n = 302) sets. Median follow-up from diagnosis was 5.8 and 6.6 years, respectively. Median plasma TIMP-1 levels were 335 and 183 ng/mL in the pilot and primary sets, respectively. Overall survival was significantly shorter with each higher tertile of TIMP-1 in both datasets (P<.001). For the primary cohort, hazard ratio of (HR) death and median survival by plasma TIMP-1 tertile levels were: low, HR 1.0, 43 months; middle, HR 1.7, 27 months; high, HR 2.4, 19 months. In the primary set, significant covariates in the adjusted Cox regression model were: TIMP-1 level (mid or high vs low tertile), prostate-specific antigen (>20 vs ≤ 20 ng/mL), alkaline phosphatase (>102 vs â102 U/L), Eastern Cooperative Oncology Group performance status (1 + vs 0), and Gleason score (7 or 8 vs ≤ 6). Conclusions: Elevated plasma TIMP-1 levels predicted decreased survival in metastatic castration-resistant PC patients, independent of known prognostic markers.

UR - http://www.scopus.com/inward/record.url?scp=79251500023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251500023&partnerID=8YFLogxK

U2 - 10.1002/cncr.25394

DO - 10.1002/cncr.25394

M3 - Article

VL - 117

SP - 517

EP - 525

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 3

ER -