非小细胞肺癌（NSCLC）通常表现出增强的分泌蛋白酸性和富含半胱氨酸（SPARC）表达。本研究旨在调查SPARC表达对转移性NSCLC患者的临床病理特征、Pembrolizumab治疗反应和预后的影响。本研究纳入了36例确诊为无可操作驱动突变的转移性NSCLC患者，并接受了Pembrolizumab联合或不联合化疗。对PD-L1和SPARC表达进行评估，根据肿瘤比例评分对PD-L1表达进行分类，将SPARC染色强度分为1+、2+和3+。比较了不同组别的患者特征，并通过二元logistic回归分析确定可能的预测标志物。未发现SPARC表达与吸烟状态、组织病理类型、T和N分期、肝脏和骨转移之间存在显著关联。高(SPARC)表达显著与较低的脑转移率呈正相关，但与较高的中枢神经系统进展率呈负相关（p=0.022和p=0.011，分别）。客观疗效率（ORR）显示SPARC 1+组患者较高的趋势（85.7% vs. 2+组的43.8%和3+组的50.0%，p=0.052）。单变量分析没有发现SPARC表达是进展无瘤生存(PFS)（p=0.7）和总生存(OS)（p=0.07）的显著预后因子。SPARC 1+表达对Pembrolizumab治疗反应产生负面影响(p=0.04，OR：0.11，95%CI：0.01-0.92)。我们的研究揭示了SPARC表达作为转移性NSCLC患者一线治疗中Pembrolizumab反应的潜在预测因子和中枢神经系统进展的标志物的新方面。Copyright © 2023 Elsevier B.V. All rights reserved.

Non-small cell lung cancer (NSCLC) often exhibits elevated Secreted Protein Acidic and Cysteine-Rich (SPARC) expression. In this study, we investigated the impact of SPARC expression on clinicopathologic features, pembrolizumab response, and prognosis in metastatic NSCLC patients.Thirty-six patients diagnosed with metastatic NSCLC without actionable driver mutation and who received pembrolizumab with or without chemotherapy were included in this study. PD-L1 and SPARC expression were evaluated, with PD-L1 expression categorized based on tumor proportion score and SPARC staining intensity graded as 1+, 2+, and 3 +. Patients' characteristics were compared across groups, and possible predictive markers were determined by binary logistic regression analysis.No significant associations were found between SPARC expression and smoking status, histopathological tumor type, T and N status, and liver and bone metastasis. Higher SPARC expression was significantly linked to lower brain metastasis rates but higher CNS progression rates (p = 0.022 and p = 0.011, respectively. The objective response rate (ORR) showed a trend of being higher in the SPARC 1 + group (85.7% vs. 43.8% and 50.0% in 2 + and 3 + groups, respectively, p = 0.052. Univariate analysis did not find SPARC expression to be a significant prognostic factor for progression-free survival (PFS) (p = 0.7) and overall survival (OS) (p = 0.07).SPARC 1 + expression negatively affected the pembrolizumab response(p = 0.04,OR:0.11, 95%CI 0.01-0.92).Our study sheds light on a novel aspect of SPARC expression as a potential predictor of pembrolizumab response and a marker for CNS progression in metastatic NSCLC patients treated in the first-line setting.Copyright © 2023 Elsevier B.V. All rights reserved.