Wu Yifan, Chen Cunte, Cui Yingwen, Zou Ruoyao, Yang Yaoxiang, Sun Fengjie, Du Yanzi, Wang Peipei
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
Front Immunol. 2025 Aug 14;16:1656242. doi: 10.3389/fimmu.2025.1656242. eCollection 2025.
Although immune checkpoint blockade (ICB) therapy has transformed the therapeutic landscape for ovarian cancer (OC), the predictive utility of immune checkpoint (IC) expression signatures in stratifying clinical outcomes requires further systematic interrogation.
Transcriptomic profiles from 147 OC patients within The Cancer Genome Atlas (TCGA) cohort were interrogated to assess the prognostic significance of ICs. These genomic findings were subsequently validated through immunohistochemical analysis of an independent institutional cohort comprising 74 OC tissue specimens.
Both TCGA and validation cohorts demonstrated that elevated expression of PD-1 and LAG-3 correlated with inferior overall survival (OS) in patients with OC. Importantly, among the ICs, PD-1/LAG-3 co-expression emerged as the optimal combinatorial biomarker, independently predicting adverse outcomes [hazard ratio (HR) = 1.74, 95% confidence interval (CI): 1.12-2.70, < 0.001]. The derived nomogram model incorporating PD-1/LAG3 status, TNM stage, histologic grade, and age generated patient-tailored 1-5 year OS rate estimates. Notably, risk stratification using this model significantly enhanced prognostic precision versus conventional parameters (TNM stage or histologic grade) alone, especially in patients with serous cystadenocarcinoma.
Elevated IC expression correlated with poor OS in OC patients. Specifically, PD-1/LAG-3 co-expression emerged as the optimal prognostic biomarker pair, representing a promising therapeutic target for dual checkpoint blockade strategies in OC.
尽管免疫检查点阻断（ICB）疗法改变了卵巢癌（OC）的治疗格局，但免疫检查点（IC）表达特征在分层临床结局中的预测效用仍需进一步系统研究。
对癌症基因组图谱（TCGA）队列中147例OC患者的转录组谱进行分析，以评估IC的预后意义。随后，通过对包含74例OC组织标本的独立机构队列进行免疫组织化学分析，验证了这些基因组学发现。
TCGA队列和验证队列均显示，PD-1和LAG-3表达升高与OC患者较差的总生存期（OS）相关。重要的是，在IC中，PD-1/LAG-3共表达成为最佳组合生物标志物，可独立预测不良结局[风险比（HR）=1.74，95%置信区间（CI）：1.12-2.70，P<0.001]。纳入PD-1/LAG3状态、TNM分期、组织学分级和年龄的衍生列线图模型可生成针对患者的1-5年OS率估计值。值得注意的是，与单独使用传统参数（TNM分期或组织学分级）相比，使用该模型进行风险分层可显著提高预后预测的准确性，尤其是在浆液性囊腺癌患者中。
IC表达升高与OC患者的OS较差相关。具体而言，PD-1/LAG-3共表达成为最佳预后生物标志物对，代表了OC中双重检查点阻断策略的一个有前景的治疗靶点。
