Chang Hao, Iizasa Toshihiko, Shibuya Kiyoshi, Iyoda Akira, Suzuki Makoto, Moriya Yasumitsu, Liu Tian-Ling, Hiwasa Takaki, Hiroshima Kenzo, Fujisawa Takehiko
Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Cancer. 2004 Apr 15;100(8):1665-72. doi: 10.1002/cncr.20156.
Angiogenesis plays a crucial role in tumor growth and metastasis. Recently, some studies have focused on the angiogenesis inhibitor endostatin. However, the biologic role of the precursor of endostatin, collagen XVIII, in human malignancy is unknown. The purpose of the current study was to evaluate whether the expression of collagen XVIII has additional prognostic value for survival in patients with nonsmall cell lung carcinoma (NSCLC).
The authors investigated the expression of collagen XVIII in 221 patients using immunohistochemical methods. To confirm the specificity of the collagen XVIII polyclonal antibody used in the current study and to test the expression of collagen XVIII in human lung carcinoma, Western blot analysis was performed on a panel of human lung carcinoma cell lines.
Collagen XVIII expression was detected in 162 of 221 patients with NSCLC (73%), primarily in the tumor cell cytoplasm. Low collagen XVIII expression levels were found in 75 tumor specimens, while high collagen XVIII expression levels were noted in 87 tumor specimens. The prevalence of positive collagen XVIII expression was greater in T2-4 tumors than in T1 tumors (P = 0.0235). The prognosis for patients with strongly collagen XVIII-positive NSCLC was significantly worse than the prognosis for patients with collagen XVIII-positive or collagen XVIII-negative NSCLC (P = 0.0010). Multivariate analysis indicated that T status, lymph node status, and the overexpression of collagen XVIII were independent prognostic factors.
The results of the current study indicated that the overexpression of collagen XVIII was associated with NSCLC progression and poor outcome. Thus, collagen XVIII expression may serve as a useful prognostic marker in patients with NSCLC.
血管生成在肿瘤生长和转移中起着关键作用。最近，一些研究聚焦于血管生成抑制剂内皮抑素。然而，内皮抑素的前体胶原蛋白 XVIII 在人类恶性肿瘤中的生物学作用尚不清楚。本研究的目的是评估胶原蛋白 XVIII 的表达对非小细胞肺癌（NSCLC）患者的生存是否具有额外的预后价值。
作者采用免疫组织化学方法研究了 221 例患者中胶原蛋白 XVIII 的表达。为了确认本研究中使用的胶原蛋白 XVIII 多克隆抗体的特异性，并检测胶原蛋白 XVIII 在人肺癌中的表达，对一组人肺癌细胞系进行了蛋白质印迹分析。
221 例 NSCLC 患者中有 162 例（73%）检测到胶原蛋白 XVIII 表达，主要在肿瘤细胞胞质中。75 个肿瘤标本中胶原蛋白 XVIII 表达水平低，而 87 个肿瘤标本中胶原蛋白 XVIII 表达水平高。T2 - 4 期肿瘤中胶原蛋白 XVIII 阳性表达的发生率高于 T1 期肿瘤（P = 0.0235）。胶原蛋白 XVIII 强阳性 NSCLC 患者的预后明显差于胶原蛋白 XVIII 阳性或阴性 NSCLC 患者（P = 0.0010）。多因素分析表明，T 分期、淋巴结状态和胶原蛋白 XVIII 的过表达是独立的预后因素。
本研究结果表明，胶原蛋白 XVIII 的过表达与 NSCLC 的进展和不良预后相关。因此，胶原蛋白 XVIII 的表达可能是 NSCLC 患者有用的预后标志物。
