Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer
Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-04-0443
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发表时间：
2004-08-15
影响因子：
11.5
通讯作者：
Fujisawa, T
中科院分区：
文献类型：
--
作者：
Iizasa, T;Chang, H;Fujisawa, T
目的：本研究的目的是确定胶原蛋白XVIII表达是否与循环血清内皮抑制素相关，以及这在非小细胞肺癌（NSCLC）患者中是否具有任何预后价值。通过竞争性酶免疫测定法定量测定血清内皮抑素水平，采用免疫组化方法检测94例手术切除的NSCLC患者肿瘤组织中胶原XVIII的表达。抗XVIII多克隆抗体免疫组化染色阳性60例（63.8%），其中强阳性11例（11.7%）。患者组的平均（+/- SD）血清内皮抑素水平为41.6 +/- 34.4 ng/ml，对照组为16.3 +/- 10.3 ng/ml（P < 0.0001）。胶原XVIII强阳性的IT患者血清内皮抑素水平显著高于胶原XVIII阴性或弱阳性的IT患者（P = 0.0297）。阴性、弱阳性和强阳性患者的5年生存率分别为77.8%、56.9%和43.8%。XVIII型胶原强阳性表达的病例的预后明显差于阴性表达的病例（P = 0.0027）。采用考克斯比例风险模型对疾病特异性生存率进行多变量分析，结果显示，（强阳性对阴性;弱阳性对阴性）、肿瘤分类和区域淋巴结分类是独立的预后因素。我们的研究结果表明，肿瘤组织中胶原XVIII的表达与NSCLC的预后不良密切相关，并与肿瘤组织中胶原XVIII的水平升高相关。循环血清内皮抑素。
Purpose: The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non-small cell lung cancer (NSCLC).Experimental Design: Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC.Results: Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (+/- SD) serum endostatin level was 41.6 +/- 34.4 ng/ml in the patient group and 16.3 +/- 10.3 ng/ml in the control group (P < 0.0001). The It cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors.Conclusions: Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin.