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.
Highlights
Prostate cancer is the most common malignancy and the second leading cause of cancer death in males in the United States [1]
We found that CCL2 induced prostate cancer cell migration (Figure 1A)
We investigated whether the changes in the mRNA levels of two important contributors to the epithelial-mesenchymal transition (EMT), androgen receptor (AR), and transforming growth factor-β1 (TGF-β1), were associated with increased autocrine CCL2 levels
Summary
Prostate cancer is the most common malignancy and the second leading cause of cancer death in males in the United States [1]. Because androgen/androgen receptor (AR) signaling promotes prostate cancer progression, standard treatment for patients with advanced prostate cancer employs androgen-deprivation therapy (ADT) [2,3,4]. Prostate cancer often progresses to castration-resistant prostate cancer (CRPC) after several years of ADT [5]. Prostate-specific antigen (PSA) is a reliable biomarker for prostate cancer, it has significant limitations [6, 7]. We previously showed that the suppression of AR signaling inhibited prostate cancer cell proliferation and PSA secretion and promoted CCL2 secretion, enabling prostate cancer cells to metastasize [8]. We investigated the validity of chemokine (CC motif) ligand 2 (CCL2) as a biomarker complementary to PSA in prostate cancer diagnosis and prognosis
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