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On-line Access: 2025-01-24

Received: 2024-03-07

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Journal of Zhejiang University SCIENCE B

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


Author(s):  Yu DONG1, Zitong YANG1, Zhinan XIA1, 2, Jiahao LIAO1, Zhiming CUI<3/sup>, Shenhao XU1, Bing LIU1, Liangliang REN1, Tengda WANG4, Wei GUO1, Shuwen WANG1, Yuyong WANG5, 6, Cheng ZHANG1

Affiliation(s):  1Department of Urology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, China; more

Corresponding email(s):  b1518118@zju.edu.cn, zhangcheng13836182568@zju.edu.cn

Key Words:  PANoptosis; ccRCC; Prognosis; Tumor immune microenvironment; Immunotherapy response


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Yu DONG1, Zitong YANG1, Zhinan XIA1,2, Jiahao LIAO1, Zhiming CUI<3/sup>, Shenhao XU1, Bing LIU1, Liangliang REN1, Tengda WANG4, Wei GUO1, Shuwen WANG1, Yuyong WANG5,6, Cheng ZHANG1. Constructing a PANoptosis-based prognostic signature to evaluate the immune landscape and therapy response in clear cell renal cell carcinoma[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2400132

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author="Yu DONG1, Zitong YANG1, Zhinan XIA1,2, Jiahao LIAO1, Zhiming CUI<3/sup>, Shenhao XU1, Bing LIU1, Liangliang REN1, Tengda WANG4, Wei GUO1, Shuwen WANG1, Yuyong WANG5,6, Cheng ZHANG1",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
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A1 - Bing LIU1
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Abstract: 
Objective: To identify PANoptosis-related genes (PRGs) in ccRCC for patient stratification and prognosis prediction. Methods: 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 LASSO and Cox regression. The PANI model, comprising PRGs, was validated through single-cell RNA sequencing (scRNA-seq), immunohistochemistry, and 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. Proliferation and migration capabilities of ZBP1 were assessed by CCK-8 and transwell assays. Results: We identified five PRGs (ZBP1, TNFSF14, CDKN3, PTHLH, and HMOX1) comprising PANI, independently associated with ccRCC patient prognosis. The PANI-based nomogram, integrated with clinical factors, demonstrated high predictive accuracy for prognosis. High-PANI patients exhibited distinct co-mutation patterns in ccRCC driver genes and lower survival probabilities, with an enriched immune-related functional profile, indicating an activated immune environment. These patients also showed increased sensitivity to immunotherapy and antineoplastic drugs. The knockdown of ZBP1, a key PRG in the PANI, significantly reduced ccRCC cell proliferation and migration. Conclusions: PANI provides precise prognosis and immunotherapy response predictions for ccRCC patients, facilitating individualized treatment strategies.

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