Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer

Abstract

// Kouji Izumi 1 , Atsushi Mizokami 1 , Hsiu-Ping Lin 2 , Hui-Min Ho 2 , Hiroaki Iwamoto 1 , Aerken Maolake 1 , Ariunbold Natsagdorj 1 , Yasuhide Kitagawa 1 , Yoshifumi Kadono 1 , Hiroshi Miyamoto 3 , Chiung-Kuei Huang 4 , Mikio Namiki 1 and Wen-Jye Lin 2 1 Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan 2 Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan 3 Departments of Pathology and Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 4 Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA Correspondence to: Kouji Izumi, email: // Wen-Jye Lin, email: // Keywords : androgen deprivation therapy; biomarker; CCL2; prostate cancer; risk classification Received : July 06, 2015 Accepted : December 04, 2015 Published : December 19, 2015 Abstract Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men ( n = 379) with and without prostate cancer. Patients with CCL2 ≥ 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ≥ 320 pg/mL and PSA ≥ 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.