Mizuguchi Shinjiro, Nishiyama Noritoshi, Iwata Takashi, Nishida Tatsuya, Izumi Nobuhiro, Tsukioka Takuma, Inoue Kiyotoshi, Uenishi Takahiro, Wakasa Kenichi, Suehiro Shigefumi
Department of Thoracic Surgery, Osaka City University Hospital, Osaka, Japan.
Lung Cancer. 2007 Dec;58(3):369-75. doi: 10.1016/j.lungcan.2007.07.002. Epub 2007 Aug 13.
This study aimed to establish the clinical significance of preoperative serum cytokeratin 19 fragment (CYFRA21-1) and Sialyl Lewis(x) (SLX) in patients with stage I non-small cell lung cancer (NSCLC). The study involved 137 patients (87 male, 50 female; median age 69 years) with completely resected stage I NSCLC. SLX, carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA21-1 were examined. Receiver operator characteristic (ROC) curves were constructed to determine prognostic cut-off values. Among the 137 patients, we identified 30 with recurrence within 3 years. The 5-year survival rates in patients with (n=30) and without (n=107) recurrence were 14% and 81%, respectively. The serum concentrations of SLX, CEA, and CYFRA21-1 in the recurrence group were significantly higher than those in the non-recurrence group. The areas under the ROC curve (AUC) were 0.72, 0.65, 0.53, and 0.64 for SLX, CEA, SCC, and CYFRA21-1, respectively. The prognostic cut-off values were 36U/ml, 7.8ng/ml, 1.5ng/ml, and 3.2ng/ml for SLX, CEA, SCC, and CYFRA21-1, respectively. A log-rank test revealed that age, performance status, T factor, lymphatic invasion, vascular invasion, SLX, CEA, SCC, and CYFRA21-1 were all significantly associated with survival. By multivariate analysis, age, performance status, lymphatic invasion, SLX (risk ratio, 4.11) and CYFRA21-1 (risk ratio, 3.47) were independent prognostic factors. For patients positive for both CYFRA21-1 and SLX, the relative risk was 5.32 compared with patients who were negative for both markers. The 5-year survival rates were 80% in the group negative for both markers (n=86); 52% in the group positive for one of the markers (n=43); and 13% for the group positive for both markers (n=8) (p<0.001). We concluded that serum SLX and CYFRA21-1 were prognostic markers for stage I NSCLC. Their combination should contribute to the classification of stage I NSCLC patients. There is a need to consider adjuvant and neoadjuvant therapies to improve prognosis in patients positive for both tumor markers.
本研究旨在确立术前血清细胞角蛋白19片段（CYFRA21-1）和唾液酸路易斯x（SLX）在Ⅰ期非小细胞肺癌（NSCLC）患者中的临床意义。该研究纳入了137例Ⅰ期NSCLC完全切除患者（男性87例，女性50例；中位年龄69岁）。检测了SLX、癌胚抗原（CEA）、鳞状细胞癌抗原（SCC）和CYFRA21-1。构建受试者工作特征（ROC）曲线以确定预后临界值。在137例患者中，我们确定30例在3年内复发。复发患者（n=30）和未复发患者（n=107）的5年生存率分别为14%和81%。复发组中SLX、CEA和CYFRA21-1的血清浓度显著高于未复发组。SLX、CEA、SCC和CYFRA21-1的ROC曲线下面积（AUC）分别为0.72、0.65、0.53和0.64。SLX、CEA、SCC和CYFRA21-1的预后临界值分别为36U/ml、7.8ng/ml、1.5ng/ml和3.2ng/ml。对数秩检验显示年龄、体能状态、T因子、淋巴侵犯、血管侵犯、SLX、CEA、SCC和CYFRA21-1均与生存显著相关。多因素分析显示，年龄、体能状态、淋巴侵犯、SLX（风险比，4.11）和CYFRA21-1（风险比，3.47）是独立的预后因素。CYFRA21-1和SLX均阳性的患者与两种标志物均阴性的患者相比，相对风险为5.32。两种标志物均阴性的组（n=86）5年生存率为80%；一种标志物阳性的组（n=43）为52%；两种标志物均阳性的组（n=8）为13%（p<0.001）。我们得出结论，血清SLX和CYFRA21-1是Ⅰ期NSCLC的预后标志物。它们的联合应用应有助于Ⅰ期NSCLC患者的分类。有必要考虑辅助和新辅助治疗以改善两种肿瘤标志物均阳性患者的预后。
