Abstract：
OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：目前缺乏预测鼻咽癌远处转移的有效生物标志物。我们旨在探讨FAP+癌相关成纤维细胞（CAFs）衍生的CXCL1在鼻咽癌中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。
方法：回顾性纳入了345例局部晚期鼻咽癌患者（训练队列：验证队列=160:185）。通过多重免疫荧光染色和免疫组织化学检测CXCL1和FAP的共表达以及PD-L1的表达。分别。主要终点是无远处转移生存期（DMFS）。采用Kaplan-Meier法计算生存率。Cox比例风险模型用于评估预后危险因素。
结果：在NPC中鉴定了CAFs中的一种新的CXCL1+_FAP表型，然后用于将患者分为低危组和高危组。在训练队列和验证队列中，高风险组患者的DMFS较差，总生存期（OS），无进展生存期(PFS)和局部区域无复发生存期(LRFS)高于低危组患者.多因素分析显示CXCL1+_FAP+表型是DMFS的独立预后因素,操作系统,PFS和LRFS。进一步结果显示，高风险组患者的PD-L1表达高于低风险组。
结论：我们的研究表明，CAFs中的CXCL1_FAP表型可以有效地将局部晚期NPC患者分为远处转移的不同风险组，可能是抗PD-1/PD-L1免疫治疗的潜在生物标志物。
方法：回顾性纳入了345例局部晚期鼻咽癌患者（训练队列：验证队列=160:185）。通过多重免疫荧光染色和免疫组织化学检测CXCL1和FAP的共表达以及PD-L1的表达。分别。主要终点是无远处转移生存期（DMFS）。采用Kaplan-Meier法计算生存率。Cox比例风险模型用于评估预后危险因素。
结果：在NPC中鉴定了CAFs中的一种新的CXCL1+_FAP表型，然后用于将患者分为低危组和高危组。在训练队列和验证队列中，高风险组患者的DMFS较差，总生存期（OS），无进展生存期(PFS)和局部区域无复发生存期(LRFS)高于低危组患者.多因素分析显示CXCL1+_FAP+表型是DMFS的独立预后因素,操作系统,PFS和LRFS。进一步结果显示，高风险组患者的PD-L1表达高于低风险组。
结论：我们的研究表明，CAFs中的CXCL1_FAP表型可以有效地将局部晚期NPC患者分为远处转移的不同风险组，可能是抗PD-1/PD-L1免疫治疗的潜在生物标志物。
