Wang Ying, Zhang Minghang, Chen Cen, Liu Yanxia, Gao Yuan, Li Hongxia, Lu Baohua, Hu Mingming, Zhang Hongmei, Lin Peter Ping, Ren Zhanliang, Zhang Tongmei, Xu Shaofa
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, China.
Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, China.
Biomark Insights. 2025 Aug 9;20:11772719251338620. doi: 10.1177/11772719251338620. eCollection 2025.
Patients with extensive disease (ED)-small cell lung cancer (SCLC) commonly suffer a more inferior prognosis than those with limited disease (LD)-SCLC.
This study aims to investigate the heterogeneity and prognostic significance of various aneuploid circulating tumor cells (CTCs) subtypes and CTC-associated white blood cell (CTC-WBC) clusters in patients with LD-and ED-SCLC respectively.
This prospective, non-interventional, single-center study included 48 patients with LD-SCLC and 47 patients with ED-SCLC.
A total of 95 SCLC patients were prospectively enrolled and serial blood samples were obtained before chemotherapy administration (t) and after 2 cycles of chemotherapy (t). Comprehensive in situ co-detection of CTCs and CTC-WBC clusters were performed in all enrolled patients.
The analysis revealed no significant difference in CTCs quantity between LD-SCLC and ED-SCLC patients ( = .610). However, significant morphologic heterogeneity in CTCs, including cell size and chromosome 8 (Chr8) ploidy in CTCs was observed between the 2 groups ( < .001 and < .001). Patients with post-therapeutic small cell CTCs ⩾ 2/6 ml or triploid CTCs ⩾ 2/6 ml exhibited reduced overall survival (OS) compared to those with small cell CTCs < 2/6 ml or triploid CTCs < 2/6 ml in the ED-SCLC ( = .011 and = .018). Additionally, the positive detection of post-therapeutic tetraploid CTCs was associated with inferior survival in both LD-and ED-SCLC ( = .041 and = .049). The presence of CTC-WBC clusters at baseline and after treatment significantly correlated with inferior OS in ED-SCLC ( = .016 and = .028) but not in LD-SCLC ( = .355 and = .621). Multivariate analysis identified brain metastasis and pre-treatment CTC-WBC clusters as independent prognostic factors for OS in ED-SCLC patients ( = .004 and = .013).
Ideal biomarkers should be more specific for survival prediction in patients with different disease stages. Pre-treatment CTC-WBC clusters can independently predict inferior OS in ED-SCLC but not LD-SCLC.
广泛期疾病（ED）-小细胞肺癌（SCLC）患者的预后通常比局限期疾病（LD）-SCLC患者更差。
本研究旨在分别调查LD-SCLC和ED-SCLC患者中各种非整倍体循环肿瘤细胞（CTC）亚型和CTC相关白细胞（CTC-WBC）簇的异质性及预后意义。
这项前瞻性、非干预性、单中心研究纳入了48例LD-SCLC患者和47例ED-SCLC患者。
共前瞻性纳入95例SCLC患者，并在化疗给药前（t）和化疗2个周期后（t）采集系列血样。对所有纳入患者进行CTC和CTC-WBC簇的全面原位共检测。
分析显示，LD-SCLC和ED-SCLC患者的CTC数量无显著差异（P = 0.610）。然而，两组之间观察到CTC存在显著的形态学异质性，包括细胞大小和CTC中的8号染色体（Chr8）倍性（P < 0.001和P < 0.001）。与ED-SCLC中细胞小的CTC < 2/6 ml或三倍体CTC < 2/6 ml的患者相比，治疗后细胞小的CTC≥2/6 ml或三倍体CTC≥2/6 ml的患者总生存期（OS）降低（P = 0.011和P = 0.018）。此外，治疗后四倍体CTC的阳性检测与LD-SCLC和ED-SCLC的较差生存率相关（P = 0.041和P = 0.049）。基线和治疗后CTC-WBC簇的存在与ED-SCLC的较差OS显著相关（P = 0.016和P = 0.028），但与LD-SCLC无关（P = 0.355和P = 0.621）。多因素分析确定脑转移和治疗前CTC-WBC簇是ED-SCLC患者OS的独立预后因素（P = 0.004和P = 0.013）。
理想的生物标志物对于不同疾病阶段患者的生存预测应更具特异性。治疗前CTC-WBC簇可独立预测ED-SCLC而非LD-SCLC的较差OS。
