Constructing a PANoptosis-based prognostic signature to evaluate the immune landscape and therapeutic response in clear cell renal cell carcinoma

作者：Yu Dong, Zitong Yang, Zhinan Xia, Jiahao Liao, Zhiming Cui, Shenhao Xu, Bing Liu, Liangliang Ren, Tengda Wang, Wei Guo, Shuwen Wang, Yuyong Wang, Cheng Zhang · 发表于：Journal of Zhejiang University SCIENCE B · 年份：2025 · DOI：10.1631/jzus.b2400132 · 研究领域：Ferroptosis and cancer prognosis、Renal cell carcinoma treatment、Inflammasome and immune disorders

To identify pyroptosis, apoptosis, and necroptosis (PANoptosis)-related genes (PRGs) in clear cell renal cell carcinoma (ccRCC) for patient stratification and prognosis prediction. We used differential expression analysis and weighted gene co-expression network analysis (WGCNA) to identify ccRCC-specific PRGs. A prognostic model, the PANoptosis-index (PANI), was constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression. The PANI model, comprising PRGs, was validated through single-cell RNA-sequencing (scRNA-seq), immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Patient cohorts were categorized into high- and low-PANI groups, and the model’s performance was appraised using various metrics. External validation was performed with the E-MTAB-1980 dataset. Functional and gene set enrichment analyses distinguished biological differences between groups. Mutational landscapes and tumor immune microenvironments were compared. Sensitivity to immunotherapy and antineoplastic drugs was also predicted using PANI. The effects of Z-DNA-binding protein 1 ( ZBP1 ) on cell proliferation and migration were assessed by cell counting kit-8 (CCK-8) and Transwell assays. We identified five PRGs ( ZBP1 , tumor necrosis factor superfamily protein 14 ( TNFSF14 ), cyclin-dependent kinase inhibitor 3 ( CDKN3 ), parathyroid hormone-like hormone ( PTHLH ), and heme-oxygenase 1 ( HMOX1 )) constituting PANI, independently as...