Urine CXCL1 as a biomarker for tumor detection and outcome prediction in bladder cancer

Subtitle:

Article type: Research Article

Authors: Nakashima, Masakazu^a | Matsui, Yoshiyuki^a | Kobayashi, Takashi^a | Saito, Ryoichi^a | Hatahira, Satoko^b | Kawakami, Kazumi^b | Nakamura, Eijiro^c | Nishiyama, Hiroyuki^d | Ogawa, Osamu^{a; *}

Affiliations: [a] Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan | [b] Toray Industries Inc., New Frontiers Research Laboratories, Kanagawa, Japan | [c] Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan | [d] Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Correspondence: [*] Corresponding author: Osamu Ogawa, Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Tel.: +81 75 751 3325; Fax: +81 75 761 3441; E-mail: ogawao@kuhp.kyoto-u.ac.jp

Abstract: BACKGROUND AND OBJECTIVE: To clarify the clinical usefulness and diagnostic accuracy of urine chemokine (C-X-C motif) ligand 1 (CXCL1) as a biomarker for tumor detection and outcome prediction in patients with bladder cancer (BCa). METHODS: We measured urine CXCL1 levels in 175 patients with BCa and 30 healthy controls. The value of urine CXCL1 concentration normalized by urine creatinine (CXCL1/Cre) was analyzed in terms of detecting bladder tumors and predicting intravesical recurrence after transurethral resection (TUR). RESULTS: CXCL1/Cre was significantly higher (3-fold) in BCa patients than in healthy participants and the difference from control samples was greater in patients with advanced BCa. Although the urine cytology test generally lost diagnostic power in patients with low-grade superficial tumors, the sensitivity of CXCL1/Cre was not compromised in this patient population. Patients with higher CXCL1/Cre were significantly more likely to develop intravesical recurrence after TUR and multivariate analysis identified CXCL1/Cre as an independent predictor of post-TUR intravesical recurrence. Importantly, CXCL1/Cre could successfully classify the probabilities of post-TUR recurrence among patients with intermediate-risk according to EORTC risk criteria into two groups equivalent to its high- and low-risk groups. CONCLUSIONS: Urine CXCL1 is a promising, non-invasive molecular marker for tumor detection and outcome prediction in patients with BCa.

Keywords: Bladder cancer, urine biomarker, sensitivity and specificity, detection, prognostic factor

DOI: 10.3233/CBM-150472

Journal: Cancer Biomarkers, vol. 15, no. 4, pp. 357-364, 2015