背景：肺癌是全球癌症死亡的首要原因，其发病率和死亡率居高不下。尽管早期非小细胞肺癌患者的五年生存率较高，但随着疾病分期的增加，患者的生存率显著下降。病理危险因素在影响Ib期非小细胞肺癌患者生存率中起着重要作用，诸如T分期、组织学亚型、血管侵犯、气腔播散等因素都被认为是关键风险因素。有研究表明病理高危因素与I期非小细胞肺癌的不良预后有关，若术前无创预测这些高危因素并规划相应的手术治疗是否可改善预后目前仍无相应研究。肿瘤干细胞作为一种潜在的治疗靶点，其在癌症进展、免疫逃逸和治疗耐药性中发挥重要作用。CD133是表征肿瘤干细胞的一个重要指标。本研究旨在评估CD133阳性循环肿瘤细胞（CD133+ CTC）在术前非侵入性评估中的潜在诊断价值，特别是其对病理高风险因素的预测能力，以辅助临床决策和改善早期NSCLC患者预后。

方法：本研究前瞻性纳入了2021年1月至2023年6月期间接受手术治疗的192例I期非小细胞肺癌患者。采用我们研究创新的一种新型基于端粒酶逆转录酶的CTC检测方法来检测CD133+ CTC水平。使用最小绝对收缩和选择算子方法和逻辑回归分析评估CD133+ CTC与病理高危因素之间的相关性并构建无创诊断预测模型。

结果：192例筛选入组患者中，术后病理证实12例患者存在病理高危因素，180例患者无病理高危因素。有病理高危因素患者的术前CD133+ CTC中位数为1.58±1.83，显著高于无病理高危因素患者的0.767±1.13（p=0.048）。通过LASSO回归筛选出六个关键变量。再经过多变量逻辑回归分析进一步确认，发现肺结节影像学特征、CEA升高和术前CD133+ CTC是预测病理高危因素的显著影响因子并建立无创预测模型。该模型的AUC为0.803，表明其具有较好的区分能力。内部bootstrap验证得到的ROC曲线、校准图和DCA图证实了该模型的准确性和预测能力。随访发现，无高危病理因素的患者PFS显著优于有高危因素的早期NSCLC患者（p=0.044）。

结论：本研究证实CD133+ CTC与病理高危因素显著相关，检测CD133+ CTC可能有助于早期NSCLC患者的治疗决策和改善预后。

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide, with persistently high incidence and mortality rates. While patients with early-stage non-small cell lung cancer (NSCLC) exhibit relatively favorable five-year survival rates, survival declines significantly with advancing disease stage. Pathological risk factors play a crucial role in determining survival outcomes in stage Ib NSCLC patients, with key determinants including T-stage, histological subtype, vascular invasion, and spread through air spaces (STAS). Existing evidence suggests that high-risk pathological features are associated with poor prognosis in stage I NSCLC. However, whether preoperative noninvasive identification of these high-risk factors and subsequent tailored surgical planning could improve outcomes remains unexplored. The noninvasive preoperative prediction of pathological risk factors remains an understudied area. Cancer stem cells (CSCs), particularly CD133+ populations, serve as potential therapeutic targets due to their roles in cancer progression, immune evasion, and treatment resistance. This study aims to evaluate the diagnostic potential of CD133+ circulating tumor cells (CTC) in preoperative noninvasive risk stratification, specifically their predictive capacity for pathological high-risk features, to inform clinical decision-making and improve outcomes in early-stage NSCLC patients. Methods: This prospective observational cohort study enrolled 192 consecutive stage I NSCLC patients who underwent surgical resection between January 2021 and June 2023. A novel telomerase reverse transcriptase-based CTC detection method developed by our team was employed to quantify CD133+ CTC. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic analysis were used to assess correlations between CD133+ CTC and pathological high-risk features, ultimately constructing a noninvasive predictive model. Results: Postoperative pathology identified pathological high-risk features in 12 patients (6.25%), while 180 patients (93.75%) were risk-factor-negative. The median preoperative CD133+ CTC count was significantly higher in high-risk patients (1.58 ± 1.83) compared to low-risk patients (0.767 ± 1.13, p=0.048). LASSO regression identified six key variables, with multivariate analysis confirming nodule characteristics, elevated CEA, and preoperative CD133+ CTC as independent predictors of pathological high-risk features. The resulting model demonstrated strong discriminative ability (AUC=0.803). Internal bootstrap validation via ROC curves, calibration plots, and decision curve analysis confirmed the model's accuracy and clinical utility. Follow-up revealed significantly better progression-free survival in low-risk patients (p=0.044). Conclusion: This study establishes CD133+ CTC as a significant factor of pathological high-risk features. CD133+ CTC detection may facilitate preoperative risk stratification and personalized treatment planning to improve outcomes in early-stage NSCLC.