Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, 438 North Jiefang Street, Zhenjiang, 212001, China.
Med Oncol. 2013 Dec;30(4):755. doi: 10.1007/s12032-013-0755-9. Epub 2013 Nov 1.
Small-cell lung caner (SCLC) is the most aggressive form of lung cancer. The aim of this study was to investigate whether the presence of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) predicts treatment response, progression-free survival (PFS), and overall survival (OS) in SCLC patients who received standard therapy. Fifty-five SCLC patients were enrolled in this single-center prospective study. CK-19 mRNA-positive CTCs in blood samples were detected using real-time quantitative-PCR assay before the initiation of chemotherapy (B0) and after one chemotherapy cycle (B1) and three chemotherapy cycles (B3). The association with known prognostic factors and the effect of CK-19 mRNA-positive CTCs on patients' prognosis were analyzed. Patients with positivity for CK-19 mRNA-positive CTCs at B0, B1, and B3 time points had shorter PFS and OS compared with patients without (P = 0.014 and P = 0.01, respectively, at B0; P = 0.008 and P = 0.002, respectively, at B1; P = 0.003 and P = 0.001, respectively, at B3). Conversion of initial positivity for CK-19 mRNA-positive CTCs to negativity at B1 and B3 time points was associated with longer PFS and OS compared with patients with persistent positivity at three time points (P = 0.008 and P = 0.010, respectively). Multivariate analysis demonstrated that the presence of CK-19 mRNA-positive CTCs at B0, B1, and B3 time points remained strong predictors of PFS and OS after adjustment for clinically significant factors. In conclusion, detection of CK-19 mRNA-positive CTCs before and during chemotherapy is an accurate indication of subsequent disease progression and mortality for SCLC patients.
小细胞肺癌（SCLC）是最具侵袭性的肺癌形式。本研究旨在探讨接受标准治疗的 SCLC 患者中，细胞角蛋白-19（CK-19）mRNA 阳性循环肿瘤细胞（CTC）的存在是否预测治疗反应、无进展生存期（PFS）和总生存期（OS）。本研究共纳入了 55 名 SCLC 患者，他们均来自单中心前瞻性研究。在化疗前（B0）、化疗 1 个周期后（B1）和 3 个周期后（B3），采用实时定量 PCR 法检测血液样本中 CK-19 mRNA 阳性 CTC。分析了其与已知预后因素的关系，以及 CK-19 mRNA 阳性 CTC 对患者预后的影响。在 B0、B1 和 B3 时间点检测到 CK-19 mRNA 阳性 CTCs 的患者与未检测到 CK-19 mRNA 阳性 CTCs 的患者相比，PFS 和 OS 更短（在 B0 时 P = 0.014 和 P = 0.01；在 B1 时 P = 0.008 和 P = 0.002；在 B3 时 P = 0.003 和 P = 0.001）。B1 和 B3 时间点初始 CK-19 mRNA 阳性 CTCs 阳性转为阴性与持续 3 个时间点阳性的患者相比，PFS 和 OS 更长（在 B1 时 P = 0.008 和 P = 0.010；在 B3 时 P = 0.003 和 P = 0.001）。多变量分析表明，在调整了临床显著因素后，B0、B1 和 B3 时间点 CK-19 mRNA 阳性 CTCs 的存在仍然是 PFS 和 OS 的强预测因子。总之，在化疗前和化疗期间检测 CK-19 mRNA 阳性 CTCs 是 SCLC 患者疾病进展和死亡的准确指标。
