Johansen Julia S, Christensen Ib J, Riisbro Rikke, Greenall Michael, Han Chen, Price Paul A, Smith Kenneth, Brünner Nils, Harris Adrian L
Connective Tissue Laboratory, Department of Rheumatology, H:S Hvidovre Hospital, Denmark.
Breast Cancer Res Treat. 2003 Jul;80(1):15-21. doi: 10.1023/A:1024431000710.
YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients with normal serum YKL-40. In the present study we evaluated the associations of preoperative serum YKL-40 in 271 patients with primary breast cancer in relation to relapse-free survival and overall survival. The median follow-up time was 5.9 years. There were 77 relapses and 69 patients died. The median serum YKL-40 concentration in the patients was 57 microg/l (range 22-688 microg/l) and significantly elevated (p < 0.0001) compared to serum YKL-40 in healthy females. Nineteen percent of the patients had high serum YKL-40 (i.e., >95 percentile of healthy females). Patients with high serum YKL-40 had shorter relapse-free interval (hazard ratio (HR) = 1.77, 95% confidence interval (CI): 1.06-2.95, p = 0.028) and overall survival (HR = 1.78, 95% CI: 1.04-3.05, p = 0.036) than patients with normal serum YKL-40. Serum YKL-40 was higher (p = 0.005) in lymph node positive patients as compared to lymph node negative patients. Multivariate analysis including lymph node status, estrogen receptor status, tumor size, age, menstrual status and serum YKL-40 showed that serum YKL-40 was an independent prognostic variable of relapse-free survival (HR = 1.73, 95% CI: 1.03-2.91, p = 0.039). Our results show that serum YKL-40 in patients with primary breast cancer at time of operation is only elevated in a small group of patients, but these patients have a shorter recurrence free interval. Further studies are required to determine the biological function of YKL-40 in breast cancer.
YKL-40是一种结缔组织细胞生长因子，可刺激内皮细胞迁移。YKL-40由癌细胞分泌，与血清YKL-40正常的患者相比，转移性乳腺癌和结直肠癌患者血清YKL-40升高与较差的预后相关。在本研究中，我们评估了271例原发性乳腺癌患者术前血清YKL-40与无复发生存率和总生存率的关系。中位随访时间为5.9年。有77例复发，69例患者死亡。患者血清YKL-40的中位浓度为57μg/l（范围22 - 688μg/l），与健康女性的血清YKL-40相比显著升高（p < 0.0001）。19%的患者血清YKL-40水平较高（即高于健康女性的第95百分位数）。血清YKL-40水平高的患者无复发生存期较短（风险比（HR）= 1.77，95%置信区间（CI）：1.06 - 2.95，p = 0.028），总生存期也较短（HR = 1.78，95% CI：1.04 - 3.05，p = 0.036），而血清YKL-40正常的患者则不然。与淋巴结阴性患者相比，淋巴结阳性患者的血清YKL-40更高（p = 0.005）。包括淋巴结状态、雌激素受体状态、肿瘤大小、年龄、月经状态和血清YKL-40在内的多变量分析表明，血清YKL-40是无复发生存率的独立预后变量（HR = 1.73，95% CI：1.03 - 2.91，p = 0.039）。我们的结果表明，原发性乳腺癌患者手术时血清YKL-40仅在一小部分患者中升高，但这些患者的无复发间隔较短。需要进一步研究以确定YKL-40在乳腺癌中的生物学功能。
