State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Lung Cancer. 2012 Jul;77(1):176-82. doi: 10.1016/j.lungcan.2012.03.001. Epub 2012 Mar 26.
To identify potential biomarkers for the prognosis of non-small cell lung cancer (NSCLC) patients by using bronchial brushing specimens.
The expression of MCM7, Ki67 and EGFR was evaluated in 494 NSCLC tissues and 174 bronchial brushings using immunohistochemical and immunocytochemical techniques. Associations between protein expression and clinico-pathologic parameters were assessed, and the impact on overall survival (OS) was analyzed.
High expression of MCM7, Ki67 and EGFR was detected in 33.3%, 23.5% and 12.7% of tissues and in 52.4%, 52.7% and 20.6% of bronchial brushings, respectively. Expression of MCM7 and Ki67 was associated with squamous cell carcinoma (SCC) in both tissues and bronchial brushings (MCM7: P = 0.0007, 0.00003; Ki67: P < 0.00001, 0.00001). Overexpression of MCM7 in tumor tissues was detected more frequently in poorly differentiated tumors (P = 0.0120) and non-bronchioloalveolar carcinomas (non-BACs) (P = 0.0238). EGFR overexpression was observed in tissues of larger tumors (P = 0.00004) and in bronchial brushings at later stage (P = 0.0262). Kaplan-Meier curves indicated that patients with overexpression of MCM7 or Ki67 had a poorer OS compared to those with low expression for all stages (P < 0.00001, 0.0233) and early-stages (P < 0.00001, 0.0032). In particular, the patients with MCM7 overexpression in bronchial brushings had a poorer prognosis (P = 0.0045). Multivariate Cox regression analysis showed that MCM7 was an independent prognostic indicator both in tissue samples and bronchial brushings.
Our data suggest that MCM7 and Ki67 in tumor tissues may be potential markers of a poor prognosis for NSCLC patients. MCM7 in bronchial brushings also showed an independent prognostic value, which may be useful when biopsies are unavailable.
通过支气管刷检标本，鉴定非小细胞肺癌（NSCLC）患者预后的潜在生物标志物。
采用免疫组化和免疫细胞化学技术，检测 494 例 NSCLC 组织和 174 例支气管刷检标本中 MCM7、Ki67 和 EGFR 的表达情况。评估蛋白表达与临床病理参数之间的关系，并分析对总生存期（OS）的影响。
组织和支气管刷检中，MCM7、Ki67 和 EGFR 的高表达率分别为 33.3%、23.5%和 12.7%，52.4%、52.7%和 20.6%。组织和支气管刷检中，MCM7 和 Ki67 的表达与鳞癌（SCC）相关（MCM7：P=0.0007，0.00003；Ki67：P<0.00001，0.00001）。肿瘤组织中 MCM7 过表达在低分化肿瘤（P=0.0120）和非细支气管肺泡癌（非 BAC）中更为常见（P=0.0238）。较大肿瘤的组织中观察到 EGFR 过表达（P=0.00004），且在支气管刷检标本中在晚期观察到（P=0.0262）。Kaplan-Meier 曲线表明，所有分期（P<0.00001，0.0233）和早期分期（P<0.00001，0.0032）患者中，MCM7 或 Ki67 过表达者的 OS 较差。特别是支气管刷检中 MCM7 过表达的患者预后较差（P=0.0045）。多变量 Cox 回归分析显示，MCM7 是组织样本和支气管刷检中独立的预后指标。
我们的数据表明，肿瘤组织中的 MCM7 和 Ki67 可能是非小细胞肺癌患者预后不良的潜在标志物。支气管刷检中的 MCM7 也具有独立的预后价值，在无法进行活检时可能有用。
