Frontiers in Immunology · Published 2026-08-04 · DOI 10.3389/fimmu.2026.1817862
Weidi Wang, Tianyi Chen, Haoyu Wang, Jiayuan Zhao, Chen Yang, Yuxiao Wu, Yujia Kong, Dan Wang, Yuan Li, Junjun Yang, Yang Xiang
IntroductionAlthough programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy have improved outcomes in high-risk choriocarcinoma, primary resistance remains a clinically important challenge without reliable predictive biomarkers.MethodsWe performed data-independent acquisition mass spectrometry (DIA-MS) on pretreatment plasma from a nested discovery subset of 30 patients, followed by enzyme-linked immunosorbent assay (ELISA) assessment of shortlisted candidates in the full cohort of 60 patients. An exploratory two-marker logistic model was developed and internally assessed in the same cohort. Exploratory tissue immunophenotyping and analyses of public tissue-transcriptomic and immunotherapy datasets were used to provide biological context.ResultsDIA-MS identified a resistance-associated plasma proteomic signature enriched in inflammatory and immunomodulatory mediators among patients with progressive disease. In the full-cohort ELISA assessment, elevated baseline plasma HLA-G and osteopontin (OPN) were associated with primary resistance. The exploratory two-marker model showed an apparent area under the receiver operating characteristic curve of 0.908. In the limited tissue subset, higher HLA-G expression tended to be associated with lower CD8-positive T-cell density, whereas higher OPN expression was associated with increased CD163-positive macrophage density. Public-dataset analyses provided supportive context for associations of HLA-G and SPP1 transcript expression with immune-related programs and unfavorable outcomes.DiscussionElevated circulating HLA-G and OPN are associated with resistance to PD-1 inhibitor plus chemotherapy in choriocarcinoma and may serve as candidate minimally invasive biomarkers for pretreatment risk stratification. Independent validation and functional investigation are required before clinical application.
Abstract from DOAJ. Public domain (CC0 1.0).
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Wang, W., Chen, T., Wang, H., et al. (2026). Integrated plasma proteomics identifies HLA-G and osteopontin as circulating biomarkers of resistance to PD-1 inhibitor plus chemotherapy in choriocarcinoma. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2026.1817862