Iizasa Toshihiko, Chang Hao, Suzuki Makoto, Otsuji Mizuto, Yokoi Sana, Chiyo Masako, Motohashi Shinichiro, Yasufuku Kazuhiro, Sekine Yasuo, Iyoda Akira, Shibuya Kiyoshi, Hiroshima Kenzo, Fujisawa Takehiko
Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Clin Cancer Res. 2004 Aug 15;10(16):5361-6. doi: 10.1158/1078-0432.CCR-04-0443.
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).
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.
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 11 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.
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.
本研究旨在确定ⅩⅧ型胶原蛋白的表达是否与循环血清内皮抑素相关，以及这对非小细胞肺癌（NSCLC）患者是否具有任何预后价值。
采用竞争性酶免疫测定法定量检测血清内皮抑素水平，并采用免疫组织化学方法对94例行NSCLC手术的患者肿瘤组织中的ⅩⅧ型胶原蛋白表达进行研究。
60例（63.8%）患者抗ⅩⅧ型胶原蛋白多克隆抗体免疫组织化学染色呈阳性，其中11例（11.7%）为强阳性染色。患者组血清内皮抑素平均水平（±标准差）为41.6±34.4 ng/ml，对照组为16.3±10.3 ng/ml（P<0.0001）。11例ⅩⅧ型胶原蛋白强阳性患者的血清内皮抑素水平显著高于阴性或弱阳性患者（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型胶原蛋白表达强阳性的患者预后明显比阴性表达患者差（P=0.0027）。采用Cox比例风险模型对疾病特异性生存进行多因素分析显示，ⅩⅧ型胶原蛋白表达（强阳性与阴性；弱阳性与阴性）、肿瘤分类和区域淋巴结分类是独立的预后因素。
我们的结果表明，肿瘤组织中ⅩⅧ型胶原蛋白的表达与NSCLC患者较差的预后密切相关，并与循环血清内皮抑素水平升高相关。
