Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Lung Cancer. 2012 Jul;77(1):162-7. doi: 10.1016/j.lungcan.2012.02.006. Epub 2012 Mar 3.
The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72 months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P = 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P = 0.047) and cN2-3 single station metastasis (P = 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.
几种癌症干细胞 (CSC) 相关标志物的表达已在非小细胞肺癌 (NSCLC) 中得到证实。本研究旨在阐明 CSC 相关标志物在接受诱导放化疗 (CRT) 的 NSCLC 患者中的临床作用。本研究纳入了 50 例接受多西他赛和顺铂联合胸部放疗序贯手术的临床诊断为 N2 或 N3 NSCLC 的患者。使用免疫组织化学染色检测手术切除标本中 CSC 相关标志物 (CD133、ALDH1、ABCG2 和 Bmi-1) 的表达。在 50 例患者中，20 例患者的病理检查中切除标本中无残留肿瘤细胞；在另外 30 例患者中评估了 CSC 相关标志物的表达及其与生存的相关性。中位随访 72 个月后，CD133 阳性或 ALDH1 阳性标本患者的 5 年总生存率明显低于 CD133 阴性和 ALDH1 阴性表达患者（分别为 44.9%和 90.0%；P = 0.042）。多因素分析显示，CD133 和 ALDH1 阴性（P = 0.047）和 cN2-3 单站转移（P = 0.03）是延长生存的独立预后因素。CRT 后 CSC 相关标志物的表达与 NSCLC 患者预后不良显著相关。考虑 CSC 相关标志物阳性的治疗策略的发展可能是进一步改善接受三联疗法患者预后的关键因素。
