Department of Radiation Oncology, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou Province, China.
Department of Spinal and Spinal Cord Rehabilitation, Guangdong Province Work Injury Rehabilitation Hospital, Guangzhou Province, China.
Oral Oncol. 2024 Oct;157:106963. doi: 10.1016/j.oraloncology.2024.106963. Epub 2024 Jul 19.
There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAPCancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression.
A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors.
A novel CXCL1_FAP phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1_FAP phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group.
Our study showed CXCL1_FAP phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.
目前缺乏有效的生物标志物来预测鼻咽癌(NPC)的远处转移。本研究旨在探索 NPC 中 FAP 阳性 Cancer-associated fibroblasts(CAFs)衍生的趋化因子 CXCL1 的表达及其对远处转移的预测价值,以及与 PD-L1 表达的相关性。
回顾性纳入 345 例局部晚期 NPC 患者(训练队列:验证队列=160:185)。通过多免疫荧光染色和免疫组织化学分别检测 CXCL1 和 FAP 的共表达以及 PD-L1 的表达。主要终点为无远处转移生存(DMFS)。Kaplan-Meier 法计算生存情况,Cox 比例风险模型评估预后危险因素。
本研究在 NPC 中鉴定出一种新型 CAFs 中的 CXCL1_FAP 表型,并将患者分为低风险组和高风险组。在训练队列和验证队列中,高风险组患者的 DMFS、总生存(OS)、无进展生存(PFS)和局部区域无复发生存(LRFS)均明显差于低风险组患者。多变量分析显示,CXCL1_FAP 表型是 DMFS、OS、PFS 和 LRFS 的独立预后因素。进一步的结果表明,高风险组患者的 PD-L1 表达高于低风险组患者。
本研究表明,CAFs 中的 CXCL1_FAP 表型可有效将局部晚期 NPC 患者分为不同的远处转移风险组,可能是抗 PD-1/PD-L1 免疫治疗的潜在生物标志物。