血浆胰岛素样生长因子结合蛋白-2 水平作为结直肠癌的诊断和预后生物标志物。
Plasma insulin-like growth factor-binding protein-2 levels as diagnostic and prognostic biomarker of colorectal cancer.
机构信息
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, No. 7, Chung-Shan S. Road, Taipei 100, Taiwan.
出版信息
J Clin Endocrinol Metab. 2010 Apr;95(4):1717-25. doi: 10.1210/jc.2009-2668. Epub 2010 Feb 15.
CONTEXT
Overexpression of IGF-II and IGF-binding protein (IGFBP)-2 has been reported in several cancers.
OBJECTIVE
We aimed to assess the roles of plasma IGF-II and IGFBP-2 levels as diagnostic and prognostic biomarkers and the impact of loss of imprinting (LOI) of IGF-II on the survival of colorectal cancer (CRC).
DESIGN
We conducted a case control and prospective cohort study for diagnostic and prognostic values, respectively.
PATIENTS AND SETTING
Plasma levels of IGF-II and IGFBP-2 were measured in 162 patients with CRC before surgery, in paired 15 patients after curative surgery, in 24 patients with advanced colon polyps, and in 114 healthy controls between 2003 and 2006 in National Taiwan University Hospital.
RESULTS
The area under the curve values of using IGFBP-2 as a diagnostic marker for advanced colon polyp and CRC were 0.654 [95% confidence interval (CI) = 0.547-0.76; P = 0.017] and 0.815 (95% CI = 0.766-0.864; P < 0.001), respectively. The sensitivity and specificity for diagnosing CRC were 80.2 and 64%, respectively, if the cutoff value of IGFBP-2 was 377 ng/ml. In the multivariate Cox proportional hazards regression model, higher IGFBP-2 levels were associated with increased risk of mortality [hazard ratio (HR) = 2.46; P = 0.017], whereas higher IGF-II levels were associated with reduced risk of mortality (HR = 0.42; P = 0.044). LOI of IGF-II was associated with increased risk of mortality (HR = 7.91; P = 0.014) in patients with stage IV disease.
CONCLUSIONS
IGFBP-2 is a potential diagnostic and prognostic biomarker of CRC. LOI of IGF-II is significantly associated with poor prognosis in patients with stage IV disease.
背景
已有研究报道,在多种癌症中 IGF-II 和 IGF 结合蛋白(IGFBP)-2 呈过表达状态。
目的
本研究旨在评估血浆 IGF-II 和 IGFBP-2 水平作为诊断和预后生物标志物的作用,以及 IGF-II 印迹丢失(LOI)对结直肠癌(CRC)患者生存的影响。
设计
本研究分别进行了病例对照和前瞻性队列研究,以评估诊断和预后价值。
患者和设置
2003 年至 2006 年,在台湾大学医院对 162 例接受手术治疗的 CRC 患者(术前)、15 例接受根治性手术的配对患者(术后)、24 例进展期结肠息肉患者和 114 例健康对照者(均为同期)检测血浆 IGF-II 和 IGFBP-2 水平。
结果
使用 IGFBP-2 作为诊断进展期结肠息肉和 CRC 的标志物,其曲线下面积(AUC)值分别为 0.654(95%置信区间 [CI] = 0.547-0.76;P = 0.017)和 0.815(95% CI = 0.766-0.864;P < 0.001)。如果 IGFBP-2 的截断值为 377ng/ml,则诊断 CRC 的敏感性和特异性分别为 80.2%和 64%。在多变量 Cox 比例风险回归模型中,较高的 IGFBP-2 水平与死亡风险增加相关(风险比 [HR] = 2.46;P = 0.017),而较高的 IGF-II 水平与死亡风险降低相关(HR = 0.42;P = 0.044)。IGF-II 的 LOI 与 IV 期疾病患者的死亡风险增加相关(HR = 7.91;P = 0.014)。
结论
IGFBP-2 是 CRC 的一种潜在诊断和预后生物标志物。IGF-II 的 LOI 与 IV 期疾病患者的不良预后显著相关。