Changes of Biochemical Markers of Bone Turnover and YKL-40 Following Hormonal Treatment for Metastatic Prostate Cancer Are Related to Survival

Abstract

Purpose: Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment. Experimental Design: Serum procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (BAP), CTX-I, andYKL-40 were determined by ELISA in a longitudinal study of 106 patients with metastatic PC during treatment with total androgen ablation or parenteral estrogen. Serum samples were collected with 3 months interval. Median observation time was 4.9 years (range, 3.6-6.2). A total of 78 patients died (64 within 7 months following the last blood sampling).Results: After 6 months treatment, serum PINP, BAP, and YKL-40 decreased (P < 0.0001), but not serum CTX-I compared with baseline values. Univariate Cox analysis showed that serum PINP at 6 months [log transformed and treated as a continuous variable; hazard ratio (HR), 2.2; P < 0.0001], serum BAP (HR, 1.8; P < 0.0001), and serum CTX-I (HR, 2.4; P < 0.0001), but not serum YKL-40 (HR, 1.4; P = 0.16) were associated with survival. Multivariate Cox analysis including the biomarkers 6 months after the start of treatment showed that Soloway score (HR, 3.9; P = 0.013), WHO tumor grade (HR, 3.9; P = 0.004), and serum PINP (HR, 2.2; P < 0.0001) were independent prognostic variables of survival. Scoring the biomarkers during treatment as time-dependent covariates in univariate Cox regression analysis showed that increases in serum PINP (HR, 2.0; P < 0.0001), BAP (HR, 2.1; P < 0.0001), and YKL-40 (HR, 2.1; P < 0.0001) were predictors of early death. Conclusions: Serial monitoring of serum PINP, BAP, CTX-I, andYKL-40 in metastatic PC patients during hormonal treatment provided information of prognosis.Prostate cancer (PC), the most frequent cancer in males, is responsible for f27,350 deaths in the United States in 2006 (1). The optimal management of patients with metastatic PC is still a question open for debate (2). The ongoing discussions reflect the fact that once patients have developed metastatic disease and the PC has become hormone refractory, the prognosis is poor (3). Bone is the most common site of PC spread and accounts for up to 80% of all PC metastases, and 85% to 100% of those who die from PC have bone metastases (3). The high frequency and poor prognosis of patients with metastatic PC emphasize the need for good biomarkers of treatment response, disease progression, and short survival to optimize treatment of PC patients.Several biomarkers (defined as physical signs or laboratory measurements that occur in association with a pathologic process or that have putative and/or prognostic utility; ref. Research.on May 11, 2018. © 2007 American Association for Cancer clincancerres.aacrjournals.org Downloaded from metastasis (5 -12). Recently, three large studies of PC patients with bone metastases showed that high serum CTX-I and NTX-I (8...

Diurnal, Weekly, and Long-Time Variation in Serum Concentrations of YKL-40 in Healthy Subjects

“…Some of the elevations in serum YKL-40 reported in cancer patients (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(24)(25)(26) are not higher than could be explained by pre-analytic conditions and methodologic and normal biological variability, but in all types of cancer, some patients have much higher levels (Fig. 1).…”

Experience with degarelix in the treatment of prostate cancer

“…In PCa, increased levels of S-ALP and bonespecific alkaline phosphatase appear to be significant predictors of early mortality [Robinson et al 2008;Johansen et al 2007;Ramankulov et al 2007;Jung et al 2004] and have been associated with progression of skeletal metastases Lorente et al 1996]. In addition, normalization of bone markers has been associated with improved overall survival [Lipton et al 2008].…”

Potential role of chitinase 3-like-1 in inflammationassociated carcinogenic changes of epithelial cells

“…In addition, several groups have reported that CHI3L1 is one of the most significant prognosis markers for cervical adenocarcinoma [58] , recurrent breast cancer [4] and metastatic breast cancer [21] , as well as advanced stages of breast cancer [59] . Interestingly, the CHI3L1 serum level could be a useful and sensitive biomarker for recurrence in locally advanced breast carcinoma [59] , ovarian carcinoma [60] , endometrial cancer [61] , squamous cell carcinoma of the head and neck [62] , metastatic prostate cancer or melanoma [63,64] , Hodgkin's lymphoma [65] and colon cancer [20] . Based on extensive research by Johansen and colleagues, CHI3L1 may be used as a novel and sensitive predictor of any cancer [66,67] .…”

“…Head and neck [18,22,62] Lung cancer (small cell carcinoma) Lung [133,134] Breast cancer Breast Colorectal cancer Colon [20,132] Kidney tumor Kidney [132,142,143] Hepatocellular carcinoma Liver [21,66] Ovarian tumor, endometrial cancer Ovary [55][56][57][58][59][60][61]133,138,139] Primary prostate cancer Prostate [23,63,144] Metastatic prostate cancer Papilloma thyroid carcinoma, thyroid tumor Thyroid [136,145] Extracellular myxoidchondrosarcoma Bone [146] Multiple myeloma Bone marrow [147,148] Hodgkin's lymphoma Lymph node [65] Malignant melanoma Melanocyte [18,64] Myxoid liposarcoma Fat cells [146] 5252 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol November 14, 2009 Volume 15 Number 42…”