Objective We quantified the pathological spatial intratumor heterogeneity (ITH) of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC). Materials and methods This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA–IIIB. To characterize the spatial ITH of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 (SHIP) for each tumor. The correlation between the SHIP values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation. Results Clinicopathological analysis showed correlations between high SHIP values and histological subtype (squamous cell carcinoma, p < .001) and vascular invasion (p = .004). Survival analysis revealed that patients with high SHIP values presented a significantly worse recurrence-free rate than those with low SHIP values (5-year RFS 26.3% vs 47.1%, p < .005). The impact of SHIP on cancer survival rates was verified through validation in an independent cohort. Moreover, high SHIP values were significantly associated with tumor recurrence in squamous cell carcinoma (5-year RFS 29.2% vs 52.8%, p < .05) and adenocarcinoma (5-year RFS 19.6% vs 43.0%, p < .01). Moreover, we demonstrated that a high SHIP value was an independent risk factor for tumor recurrence. Conclusions We presented an image analysis model to quantify the spatial ITH of protein expression in tumor tissues. This model demonstrated that the spatial ITH of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.

中文翻译：

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程序性死亡配体1表达的空间异质性预测已切除非小细胞肺癌的不良预后

目的 我们量化了程序性死亡配体 1 (PD-L1) 表达的病理空间肿瘤内异质性 (ITH)，并研究了其与手术切除的非小细胞肺癌 (NSCLC) 患者预后的相关性。材料和方法本研究纳入了 239 例连续手术切除的病理阶段 IIA-IIIB 的 NSCLC 标本。为了表征 NSCLC 组织中 PD-L1 表达的空间 ITH，我们开发了基于纹理图像分析的数学模型，并确定了每个肿瘤的 PD-L1 (SHIP) 的空间异质性指数。分析 SHIP 值与临床病理特征（包括预后）之间的相关性。此外，还分析了 70 个病例的独立队列以进行模型验证。结果 临床病理学分析显示高 SHIP 值与组织学亚型（鳞状细胞癌，p < .001）和血管侵犯（p = .004）之间存在相关性。生存分析显示，SHIP 值高的患者的无复发率明显低于 SHIP 值低的患者（5 年 RFS 26.3% vs 47.1%，p < .005）。SHIP 对癌症生存率的影响通过独立队列的验证得到验证。此外，高 SHIP 值与鳞状细胞癌（5 年 RFS 29.2% vs 52.8%，p < .05）和腺癌（5 年 RFS 19.6% vs 43.0%，p < .01）的肿瘤复发显着相关。 ）。此外，我们证明高 SHIP 值是肿瘤复发的独立危险因素。结论 我们提出了一种图像分析模型来量化肿瘤组织中蛋白质表达的空间 ITH。该模型表明，手术切除的 NSCLC 中 PD-L1 表达的空间 ITH 可以预测患者的不良预后。