Albert Jeffrey M, Gonzalez Adriana, Massion Pierre P, Chen Heidi, Olson Sandra J, Shyr Yu, Diaz Roberto, Lambright Eric S, Sandler Alan, Carbone David P, Putnam Joe B, Johnson David H, Lu Bo
Department of Radiation Oncology, Vanderbilt University, 1301 Medical Center Drive, B-902 The Vanderbilt Clinic, Nashville, TN 37232-5671, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1845-51. doi: 10.1158/1055-9965.EPI-07-0146.
Clusterin is a glycoprotein that has been implicated in many processes, including apoptosis, cell cycle regulation, and DNA repair. Previous studies have examined the prognostic value of clusterin expression in various malignancies. In the present study, we examined clusterin staining in tumors resected from patients with non-small cell lung cancer (NSCLC).
Tumor specimens were obtained for 113 patients with completely resected NSCLC from paraffin-embedded tissue microarrays and stained with an antibody specific for clusterin. Staining patterns were observed and graded based on intensity and then correlated with clinical data.
Positive cytoplasmic clusterin staining was observed in 44 patients, and weak/negative staining was observed in 62 patients. Patients who had tumors that stained positive for cytoplasmic clusterin had significantly longer survival in multivariate analysis (hazard ratio 0.487, 95% confidence interval 0.27-0.89). A correlation was also observed for recurrence-free survival, which approached statistical significance (hazard ratio 0.345, 95% confidence interval 0.12-1.02). In univariate analysis, patients with clusterin-positive tumors had a 63% 3-year survival, whereas patients with clusterin-negative tumors had a 42% 3-year survival (P = 0.0108); clusterin-positive tumors also had significantly less recurrence (P = 0.0231).
Cytoplasmic clusterin staining is present in a substantial number of NSCLC tumors and may be a biomarker for longer survival in patients with surgically resected NSCLC.
簇集素是一种糖蛋白，参与了许多过程，包括细胞凋亡、细胞周期调控和DNA修复。先前的研究已经探讨了簇集素表达在各种恶性肿瘤中的预后价值。在本研究中，我们检测了非小细胞肺癌（NSCLC）患者切除肿瘤中的簇集素染色情况。
从石蜡包埋的组织微阵列中获取113例完全切除的NSCLC患者的肿瘤标本，并用针对簇集素的特异性抗体进行染色。观察染色模式并根据强度进行分级，然后与临床数据相关联。
44例患者观察到细胞质簇集素阳性染色，62例患者观察到弱阳性/阴性染色。在多变量分析中，细胞质簇集素染色阳性的肿瘤患者生存期显著更长（风险比0.487，95%置信区间0.27 - 0.89）。无复发生存期也观察到相关性，接近统计学意义（风险比0.345，95%置信区间0.12 - 1.02）。在单变量分析中，簇集素阳性肿瘤患者的3年生存率为63%，而簇集素阴性肿瘤患者的3年生存率为42%（P = 0.0108）；簇集素阳性肿瘤的复发也显著更少（P = 0.0231）。
大量NSCLC肿瘤中存在细胞质簇集素染色，它可能是手术切除的NSCLC患者生存期更长的生物标志物。
