Du Wei, Zhan Jianhua, Wu Kai, Wang Yanming, Zhang Li, Hong Shaodong
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Biomark Res. 2025 May 24;13(1):76. doi: 10.1186/s40364-025-00791-1.
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC), yet durable responses remain limited in a subset of patients. Serum amyloid A (SAA), an acute-phase protein linked to systemic inflammation, may reflect dynamic immune responses. This retrospective study analyzed 242 advanced NSCLC patients treated with first-line chemoimmunotherapy or immunotherapy between August 2016 and December 2024. Patients were stratified by early SAA kinetics into flare-responders (initial rise followed by decline), responders (sustained decline), and non-responders. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan-Meier and Cox regression analyses. In the chemoimmunotherapy cohort, SAA flare-responders demonstrated significantly prolonged median PFS (29.8 months, 95% CI: 9.95-49.65; HR: 0.31, 95% CI: 0.15-0.64; p < 0.01) compared to non-responders (7.4 months, 95% CI: 4.67-10.13). Similarly, in the immunotherapy cohort, SAA flare-responders showed superior PFS. (19.9 vs. 2.1 months, HR 0.31, p < 0.01). Multivariate analysis confirmed early SAA kinetics as an independent prognostic factor for both PFS and OS in both treatment groups. Early SAA kinetics serve as a promising non-invasive biomarker for predicting clinical outcomes in advanced NSCLC treated with first-line chemoimmunotherapy or immunotherapy. These findings highlight SAA kinetics as a potential non-invasive biomarker and monitoring SAA dynamics may aid in identifying patients with higher likelihood of clinical benefit; however, prospective studies are required to determine its utility in guiding therapeutic decisions.
免疫检查点抑制剂（ICIs）已经改变了晚期非小细胞肺癌（NSCLC）的治疗格局，但仍有一部分患者的持久缓解率有限。血清淀粉样蛋白A（SAA）是一种与全身炎症相关的急性期蛋白，可能反映动态免疫反应。这项回顾性研究分析了2016年8月至2024年12月期间接受一线化疗免疫疗法或免疫疗法治疗的242例晚期NSCLC患者。根据早期SAA动力学将患者分为爆发反应者（最初上升随后下降）、反应者（持续下降）和无反应者。使用Kaplan-Meier和Cox回归分析评估临床结局，包括无进展生存期（PFS）和总生存期（OS）。在化疗免疫疗法队列中，与无反应者（7.4个月，95%CI：4.67-10.13）相比，SAA爆发反应者的中位PFS显著延长（29.8个月，95%CI：9.95-49.65；HR：0.31，95%CI：0.15-0.64；p<0.01）。同样，在免疫疗法队列中，SAA爆发反应者显示出更好的PFS。（19.9对2.1个月，HR 0.31，p<0.01）。多变量分析证实，早期SAA动力学是两个治疗组中PFS和OS的独立预后因素。早期SAA动力学是预测一线化疗免疫疗法或免疫疗法治疗的晚期NSCLC临床结局的有前景的非侵入性生物标志物。这些发现强调SAA动力学作为一种潜在的非侵入性生物标志物，监测SAA动态可能有助于识别更有可能从临床中获益的患者；然而，需要进行前瞻性研究以确定其在指导治疗决策中的效用。
