Cheeloo College of Medicine, Shandong University Cancer Center, Jinan, Shandong, China; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Int J Radiat Oncol Biol Phys. 2024 Sep 1;120(1):89-101. doi: 10.1016/j.ijrobp.2024.02.048. Epub 2024 Mar 5.
PURPOSE: Stereotactic body radiation therapy (SBRT) versus surgery for operable early-stage non-small cell lung cancer (ES-NSCLC) remains highly debated. Herein, we used spatial proteomics to identify whether any molecular biomarker(s) associate with the efficacy of either modality, in efforts to optimize treatment selection between surgery and SBRT for this population. METHODS AND MATERIALS: We evaluated biopsy tissue samples from 44 patients with ES-NSCLC treated with first-line SBRT (cohort 1) by GeoMx Digital Spatial Profiling (DSP) with a panel of 70 proteins in 5 spatial molecular compartments: tumor (panCK+), leukocyte (CD45+), lymphocyte (CD3+), macrophage (CD68+), and stroma (α-SMA+). To validate the findings in cohort 1, biopsy samples from 52 patients with ES-NSCLC who received SBRT (cohort 2) and 62 patients with ES-NSCLC who underwent surgery (cohort 3) were collected and analyzed by multiplex immunofluorescence (mIF). RESULTS: In cohort 1, higher CD44 expression in the lymphocyte compartment was associated with poorer recurrence-free survival (RFS) (DSP: P < .001; mIF: P < .001) and higher recurrence rate (DSP: P = .001; mIF: P = .004). mIF data from cohort 2 validated these findings (P < .05 for all). From cohort 3, higher lymphocyte CD44 predicted higher RFS after surgery (P = .003). Intermodality comparisons demonstrated that SBRT was associated with significantly higher RFS over surgery in CD44-low patients (P < .001), but surgery was superior to SBRT in CD44-high cases (P = .016). CONCLUSIONS: Lymphocyte CD44 may not only be a predictor of SBRT efficacy in this population but also an important biomarker (pending validation by large prospective data) that could better sharpen selection for SBRT versus surgery in ES-NSCLC.
目的：立体定向体部放射治疗（SBRT）与手术治疗可手术的早期非小细胞肺癌（ES-NSCLC）仍然存在很大争议。在此，我们使用空间蛋白质组学来确定是否有任何分子生物标志物与这两种治疗方式的疗效相关，以便为该人群的手术和 SBRT 治疗选择提供优化。
方法和材料：我们通过 GeoMx 数字空间分析（DSP）评估了 44 名接受一线 SBRT 治疗的 ES-NSCLC 患者的活检组织样本（队列 1），该分析使用了 70 个蛋白的面板，分为 5 个空间分子区室：肿瘤（panCK+）、白细胞（CD45+）、淋巴细胞（CD3+）、巨噬细胞（CD68+）和基质（α-SMA+）。为了验证队列 1 中的发现，我们收集了接受 SBRT（队列 2）的 52 名 ES-NSCLC 患者和接受手术治疗（队列 3）的 62 名 ES-NSCLC 患者的活检样本，并进行了多重免疫荧光（mIF）分析。
结果：在队列 1 中，淋巴细胞区室中 CD44 的高表达与无复发生存率（RFS）较差相关（DSP：P <.001；mIF：P <.001）和更高的复发率（DSP：P =.001；mIF：P =.004）。队列 2 的 mIF 数据验证了这些发现（所有 P <.05）。来自队列 3 的数据表明，淋巴细胞 CD44 较高可预测手术后更高的 RFS（P =.003）。亚组间比较显示，在 CD44 低表达患者中，SBRT 与手术相比具有显著更高的 RFS（P <.001），但在 CD44 高表达患者中，手术优于 SBRT（P =.016）。
结论：淋巴细胞 CD44 不仅可能是该人群中 SBRT 疗效的预测因子，而且还是一个重要的生物标志物（有待大型前瞻性数据验证），这可能会更好地优化 ES-NSCLC 中 SBRT 与手术的选择。
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