New York University School of Medicine, Department of Cardiothoracic Surgery, 530 First Ave, Suite 9V, New York, NY 10016. USA.
J Clin Oncol. 2010 Feb 20;28(6):936-41. doi: 10.1200/JCO.2009.25.5711. Epub 2010 Jan 19.
PURPOSE Plasma osteopontin (OPN) levels in advanced non-small-cell lung cancer (NSCLC) correlate with therapeutic response and survival, but the utility of plasma OPN for diagnosis and monitoring of early-stage NSCLC has not been investigated. We hypothesize that plasma OPN levels are elevated in early-stage NSCLC and decrease with resection. PATIENTS AND METHODS Presurgery plasma OPN levels (in ng/mL) were measured by enzyme-linked immunosorbent assay (ELISA) in a discovery set of 60 patients with early-stage NSCLC and were compared with data from 56 cancer-free smokers. Presurgery OPN was validated in an independent cohort of 96 patients with resectable NSCLC. The presurgery levels in the latter cohort were compared with matched postsurgery levels. Perioperative OPN levels were correlated with demographics, tumor characteristics, and perioperative events. OPN was monitored during follow-up. Results Discovery set presurgery NSCLC OPN (271 +/- 31 ng/mL) was higher than smokers (40 +/- 2 ng/mL; P = .001). Presurgery OPN was similar in the NSCLC validation cohort (324 ng/mL +/- 20 ng/mL; P = .134). Postsurgery OPN (256 ng/mL +/- 21 ng/mL) measured at mean of 9.8 weeks (range, 2 to 46 weeks) was lower than presurgery OPN (P = .005). Time from surgery significantly impacted postsurgery OPN: OPN < or = 6 weeks postsurgery (303 n/mL +/- 26 ng/mL) was higher than OPN greater than 6 weeks postsurgery (177 ng/mL +/- 29 ng/mL; P = .003). Multivariate analysis noted correlations between albumin and creatinine to presurgery OPN and use of thoracotomy to postsurgery OPN. Recurrence rate was 5% at 29 weeks mean follow-up. OPN at recurrence was elevated from postsurgery nadir. CONCLUSION Plasma OPN levels are elevated in early-stage NSCLC. They are reduced after resection and appear to increase with recurrence. Plasma OPN may have utility as a biomarker in early-stage NSCLC.
晚期非小细胞肺癌(NSCLC)患者的血浆骨桥蛋白(OPN)水平与治疗反应和生存相关,但尚未研究血浆 OPN 用于诊断和监测早期 NSCLC 的效用。我们假设早期 NSCLC 患者的血浆 OPN 水平升高,并随切除而降低。
通过酶联免疫吸附试验(ELISA)检测 60 例早期 NSCLC 患者术前血浆 OPN 水平(ng/ml),并与 56 例无癌吸烟者的数据进行比较。在可切除 NSCLC 的 96 例独立患者队列中验证了术前 OPN。后者队列的术前水平与匹配的术后水平进行了比较。围手术期 OPN 水平与人口统计学、肿瘤特征和围手术期事件相关。监测 OPN 随访期间的变化。
发现组术前 NSCLC OPN(271±31ng/ml)高于吸烟者(40±2ng/ml;P=0.001)。NSCLC 验证队列的术前 OPN 相似(324ng/ml±20ng/ml;P=0.134)。平均 9.8 周(范围 2 至 46 周)测量的术后 OPN(256ng/ml±21ng/ml)低于术前 OPN(P=0.005)。从手术到术后 OPN 的时间显著影响:术后 OPN≤6 周(303n/ml±26ng/ml)高于术后 OPN>6 周(177ng/ml±29ng/ml;P=0.003)。多变量分析注意到术前 OPN 与白蛋白和肌酐相关,术后 OPN 与开胸术相关。平均 29 周的随访中有 5%的复发率。复发时 OPN 从术后最低点升高。
早期 NSCLC 患者的血浆 OPN 水平升高。切除后降低,似乎随复发而升高。血浆 OPN 可能作为早期 NSCLC 的生物标志物具有效用。