ArticleFrontiers in oncology2022
Computational Characterizing Necroptosis Reveals Implications for Immune Infiltration and Immunotherapy of Hepatocellular Carcinoma.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 3 citations in OpenAlex.
- Comprehensive bioinformatic analysis reveals sorafenib response-related prognostic signature in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2025Article
- Construction and immunohistochemical validation of a necroptosis-related prognostic signature in bladder cancer and its association with tumor immune infiltration.Frontiers in genetics · 2025Article
- Modulating the Cell Death Immune Response for Electroporation Treatments.Bioelectricity · 2024Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
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Abstract
Necroptosis is a programmed form of necrotic cell death in regulating cancer ontogenesis, progression, and tumor microenvironment (TME) and could drive tumor-infiltrating cells to release pro-inflammatory cytokines, incurring strong immune responses. Nowadays, there are few identified biomarkers applied in clinical immunotherapy, and it is increasingly recognized that high levels of tumor necroptosis could enhance the response to immunotherapy. However, comprehensive characterization of necroptosis associated with TME and immunotherapy in Hepatocellular carcinoma (HCC) remains unexplored. Here, we computationally characterized necroptosis landscape in HCC samples from TCGA and ICGA cohorts and stratified them into two necroptosis clusters (A or B) with significantly different characteristics in clinical prognosis, immune cell function, and TME-landscapes. Additionally, to further evaluate the necroptosis levels of each sample, we established a novel necroptosis-related gene score (NRGscore). We further investigated the TME, tumor mutational burden (TMB), clinical response to immunotherapy, and chemotherapeutic drug sensitivity of HCC subgroups stratified by the necroptosis landscapes. The NRGscore is robust and highly predictive of HCC clinical outcomes. Further analysis indicated that the high NRGscore group resembles the immune-inflamed phenotype while the low score group is analogous to the immune-exclusion or metabolism phenotype. Additionally, the high NRGscore group is more sensitive to immune checkpoint blockade-based immunotherapy, which was further validated using an external HCC cohort, metastatic melanoma cohort, and advanced urothelial cancer cohort. Besides, the NRGscore was demonstrated as a potential biomarker for chemotherapy, wherein the high NRGscore patients with more tumor stem cell composition could be more sensitive to Cisplatin, Doxorubicin, Paclitaxel-based chemotherapy, and Sorafenib therapy. Collectively, a comprehensive characterization of the necroptosis in HCC suggested its implications for predicting immune infiltration and response to immunotherapy of HCC, providing promising strategies for treatment.
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