Qu Ziting, Zhang Yan, Lu Lili, Qi Xiaowen, Zhang Tengteng, Zhao Zhiyan, Zhang Yiyin, Gu Kangsheng
Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
J Cancer. 2025 Jul 28;16(11):3473-3484. doi: 10.7150/jca.114975. eCollection 2025.
To investigate the use of heat shock protein 90alpha (HSP90α) as a marker for prognostic evaluation and efficacy monitoring in patients receiving PD-1 inhibitors treatment for advanced gastric cancer (AGC). We investigated the value of HSP90α in AGC patients treated with PD-1 inhibitors from a clinical perspective using human plasma samples. In summary, plasma HSP90α was significantly associated with neutrophil-to-lymphocyte (NLR) in AGC patients at baseline. Regarding short-term efficacy, HSP90α levels decreased considerably after PD-1 inhibitor treatment in the partial response (PR) group (P=0.016). Furthermore, there was no significant difference between HSP90α levels in stable disease (SD) group before and after immunotherapy (P=0.659). However, HSP90α levels were considerably greater in AGC patients at disease progression and eventual PD-1 inhibitor therapy failure compared to baseline (P=0.041, P=0.005). Notably, plasma HSP90α, treatment lines, metastatic sites, and NLR level were independent predictive variables for overall survival (OS) in AGC patients receiving PD-1 inhibitors treatment before and after propensity score matching. Additionally, we constructed the nomogram model depending on the above independent prognostic variables, which can well differentiate the clinical prognosis of patients (P<0.001). And ROC curves, calibration curves, and decision curve analysis curves revealed promising discrimination and accuracy of the nomogram. Finally, plasma HSP90α showed specific prognostic value in different subgroups of clinical characteristics. Plasma HSP90α can be used as a marker for efficacy monitoring and prognostic assessment in AGC patients receiving PD-1 inhibitors treatment. We combined plasma HSP90α, NLR, and clinical characteristics to construct a nomogram for predicting the prognosis of gastric cancer immunotherapy, providing a powerful tool for clinical decision-making.
探讨热休克蛋白90α（HSP90α）作为晚期胃癌（AGC）患者接受PD-1抑制剂治疗时预后评估和疗效监测标志物的应用。我们从临床角度，利用人血浆样本研究HSP90α在接受PD-1抑制剂治疗的AGC患者中的价值。总之，基线时AGC患者血浆HSP90α与中性粒细胞与淋巴细胞比值（NLR）显著相关。关于短期疗效，部分缓解（PR）组患者接受PD-1抑制剂治疗后HSP90α水平显著下降（P = 0.016）。此外，疾病稳定（SD）组患者免疫治疗前后HSP90α水平无显著差异（P = 0.659）。然而，与基线相比，疾病进展和最终PD-1抑制剂治疗失败的AGC患者HSP90α水平显著更高（P = 0.041，P = 0.005）。值得注意的是，在倾向评分匹配前后，接受PD-1抑制剂治疗的AGC患者中，血浆HSP90α、治疗线数、转移部位和NLR水平是总生存期（OS）的独立预测变量。此外，我们根据上述独立预后变量构建了列线图模型，该模型能很好地区分患者的临床预后（P<0.001）。ROC曲线、校准曲线和决策曲线分析曲线显示列线图具有良好的区分度和准确性。最后，血浆HSP90α在不同临床特征亚组中显示出特定的预后价值。血浆HSP90α可作为接受PD-1抑制剂治疗的AGC患者疗效监测和预后评估的标志物。我们结合血浆HSP90α、NLR和临床特征构建了预测胃癌免疫治疗预后的列线图，为临床决策提供了有力工具。
