CCL11 (eotaxin-1): a new diagnostic serum marker for prostate cancer

Abstract

Background: The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer.

Methods: Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of <10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA.

Results: Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (P < 0.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (P < 0.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status.

Conclusions: Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values.

Figure 1. Serum CCL11 levels increase the diagnostic utility of serum PSA and PCPTRC risk analysis to predict prostate cancer

Receiver-Operator Curves demonstrating the ability of serum PSA, PCPTRC (PCTP), and serum CCL11, alone or in combination, to predict prostate cancer on patients with serum PSA <10 ng/ml (N=272). The Area Under the Curve (AUC) for each measure is indicated in parentheses.