title: Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer.
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.
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Hsiu-Ping
authors.initials: HP
authors.lastname: Lin
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Ho
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Aerken
authors.initials: A
authors.lastname: Maolake
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Ariunbold
authors.initials: A
authors.lastname: Natsagdorj
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kadono
authors.affiliation: Departments of Pathology and Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Chiung-Kuei
authors.initials: CK
authors.lastname: Huang
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Wen-Jye
authors.initials: WJ
authors.lastname: Lin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D012333:RNA, Messenger
keywords: CCL2; androgen deprivation therapy; biomarker; prostate cancer; risk classification