---
title: "Necroptosis in Cervical Cancer: Transcriptomic Consensus, Prognostic Signatures, and Therapeutic I"
id: "pubmed-42859938"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42859938"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42859938/"
doi: "10.1007/s10495-026-02440-w"
published_at: "2026-10-11T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Necroptosis in Cervical Cancer: Transcriptomic Consensus, Prognostic Signatures, and Therapeutic I
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42859938
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42859938/)
- **DOI:** [10.1007/s10495-026-02440-w](https://doi.org/10.1007%2Fs10495-026-02440-w)
- **Published At:** 2026-10-11T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This systematic review and transcriptomic cross-study consensus analysis evaluated the role of **necroptosis** in cervical cancer and its potential to improve tumor immunogenicity and therapy response. - Following PRISMA guidelines, the authors reviewed seven published prognostic models that used RNA sequencing and LASSO-based feature selection to derive necroptosis-related risk scores. - A comparative analysis identified eight overlapping genes across studies and highlighted seven necroptosis-related genes repeatedly reported; details of the exact gene names and coefficients were reported in the source. - Many identified genes are functionally connected to **mitochondrial transport and permeability**, **reactive oxygen species (ROS) generation**, and **inflammatory signaling**, indicating mechanistic links between necroptosis and cellular stress and immune pathways. - Across the integrated analyses, necroptosis activation was generally associated with increased **immune infiltration and activation** in tumors and correlated with improved prognosis in cervical cancer cohorts analyzed. - The authors synthesized existing signatures with exploratory transcriptomic analyses to propose mechanistic interactions and potential therapeutic targets aimed at modulating necroptotic signaling. - The study positions necroptosis as a promising target for combination strategies to convert immunologically “cold” cervical tumors into more responsive phenotypes, potentially enhancing synergy with **immunotherapy**. - The review produced a hypothetical cell signaling and interaction diagram and emphasized that experimental validation and therapeutic development remain necessary next steps. - The authors declared no competing interests; full methodological details, gene lists, and coefficients were reported in the original article and references. - Overall, the analysis provides a transcriptomics-based foundation for further preclinical and clinical work targeting necroptosis in cervical cancer management.
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Affiliations Expand ### Affiliations * 1 Department of Radiation Oncology, Amsterdam UMC, Amsterdam, The Netherlands. * 2 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands. * 3 Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands. * 4 Department of Experimental Immunology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands. * 5 Department of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, The Netherlands. j.tromp@amsterdamumc.nl. * 6 Department of Radiation Oncology, Amsterdam UMC, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl. * 7 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl. * 8 Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl. # Contributed equally. * PMID: **42859938** * DOI: [ 10.1007/s10495-026-02440-w ](https://doi.org/10.1007/s10495-026-02440-w) Item in Clipboard # Necroptosis as a key player in cervical cancer progression and management: a systematic review and transcriptomic cross-study consensus analysis Seth-Frerich Fobian et al. Apoptosis. 2026. Show details Display options Display options Format Abstract PubMed PMID Apoptosis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Apoptosis%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Apoptosis%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42859938/) . 2026 Oct 11;31(11):244. doi: 10.1007/s10495-026-02440-w. ### Authors [Seth-Frerich Fobian](https://pubmed.ncbi.nlm.nih.gov/?term=Fobian+SF&cauthor_id=42859938)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-1 "Department of Radiation Oncology, Amsterdam UMC, Amsterdam, The Netherlands.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-2 "Laboratory for Experimental Oncology and Radiobiology \(LEXOR\), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-3 "Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands."), [Eric Eldering](https://pubmed.ncbi.nlm.nih.gov/?term=Eldering+E&cauthor_id=42859938)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-4 "Department of Experimental Immunology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Lymphoma and Myeloma Center Amsterdam \(LYMMCARE\), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands."), [Jacqueline Tromp](https://pubmed.ncbi.nlm.nih.gov/?term=Tromp+J&cauthor_id=42859938)[#](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-equal-contrib-explanation "Contributed equally")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-5 "Department of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, The Netherlands. j.tromp@amsterdamumc.nl."), [Arlene L Oei](https://pubmed.ncbi.nlm.nih.gov/?term=Oei+AL&cauthor_id=42859938)[#](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-equal-contrib-explanation "Contributed equally")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-6 "Department of Radiation Oncology, Amsterdam UMC, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-7 "Laboratory for Experimental Oncology and Radiobiology \(LEXOR\), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42859938/#short-view-affiliation-8 "Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl.") ### Affiliations * 1 Department of Radiation Oncology, Amsterdam UMC, Amsterdam, The Netherlands. * 2 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands. * 3 Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands. * 4 Department of Experimental Immunology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands. * 5 Department of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, The Netherlands. j.tromp@amsterdamumc.nl. * 6 Department of Radiation Oncology, Amsterdam UMC, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl. * 7 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC and University of Amsterdam, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl. * 8 Cancer Biology and Immunology, Cancer Center Amsterdam, Amsterdam, The Netherlands. a.l.oei@amsterdamumc.nl. # Contributed equally. * PMID: **42859938** * DOI: [ 10.1007/s10495-026-02440-w ](https://doi.org/10.1007/s10495-026-02440-w) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Immunotherapy has improved outcomes for a subset of patients with locally advanced cervical cancer. However, many tumors remain immunologically "cold" and fail to respond. Strategies that enhance tumor immunogenicity are therefore of increasing interest. Necroptosis, a regulated form of inflammatory cell death, has emerged as a potential mechanism capable of promoting the anti-tumor immune responses through the release of damage-associated molecular patterns and enhanced antigen presentation. In this study, we performed a systematic review and transcriptomic cross-study consensus analysis of all studies carried out describing the role and mechanisms of necroptosis occurrence in cervical cancers. We analyzed all published necroptosis-related prognostic gene signatures and integrated these findings into an exploratory transcriptomic analyses to identify mechanistic insights into interlinked biological pathways, and potential therapeutic targets. Following PRISMA guidelines, we analyzed seven published prognostic models, from studies using RNA sequencing and least absolute shrinkage and selection operator (LASSO)-based feature selection to generate a prognostic risk score for patients. We then conducted a comparative analyses of eight overlapping genes and their reported risk score coefficients. Across studies, seven necroptosis-related genes were identified, many of which are functionally linked to mitochondrial transport and permeability regulation, reactive oxygen species (ROS) generation, and inflammatory signaling. Overall, our findings support a key role for necroptosis in cervical cancer, where activation thereof is generally associated with enhanced immune infiltration and activation; thereby improved prognosis. These findings position necroptosis as a promising target for combination therapy strategies aimed at converting immunologically "cold" tumors into more responsive phenotypes. By integrating published signatures with exploratory analyses, we identify potential avenues to modulate necroptotic signaling in ways that may enhance synergy with immunotherapies, and have synthesized a hypothetical cell signaling and interaction diagram. Collectively, this work provides a foundation for future experimental validation and therapeutic development. **Keywords:** Immunogenic cell death; Interactome; Cervical cancer; Necroptosis; Prognostic transcriptomics; Programmed cell death. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Competing interests: The authors declare no competing interests. ## References 1. 1. Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R et al (2021) Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med 385(20):1856–1867 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34534429/) - [DOI](https://doi.org/10.1056/nejmoa2112435) 2. 1. Mei X, Fobian SF, Crezee MIJ, van Bochove J, van Lonkhuijzen GGW (2025) High human papillomavirus viral load and local immune dysregulation are associated with poor clinical outcomes in patients with cervical cancer. Int J Gynecol Cancer 35(7):101924 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/40449175/) - [DOI](https://doi.org/10.1016/j.ijgc.2025.101924) 3. 1. Samare-Najaf M, Samareh A, Savardashtaki A, Khajehyar N, Tajbakhsh A, Vakili S et al (2024) Non-apoptotic cell death programs in cervical cancer with an emphasis on ferroptosis. Crit Rev Oncol Hematol 194:104249 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38145831/) - [DOI](https://doi.org/10.1016/j.critrevonc.2023.104249) 4. 1. Morgan MJ, Kim YS (2025) RIPK3 in necroptosis and cancer. Mol Cells 48(5):100199 - [PubMed](https://pubmed.ncbi.nlm.nih.gov/40010643/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/11938148/) - [DOI](https://doi.org/10.1016/j.mocell.2025.100199) 5. 1. Berghe TV, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P (2014) Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 15(2):135–147 - [DOI](https://doi.org/10.1038/nrm3737) Show all 120 references ## Publication types * Systematic Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Systematic+Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Systematic+Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42859938/) ## MeSH terms * Disease Progression Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Disease+Progression%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Disease+Progression) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42859938/) * Female Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Female) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42859938/) * Gene Expression Profiling Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gene+Expression+Profiling%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Gene+Expression+Profiling) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42859938/) * Gene Expression Regulation, Neoplastic Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gene+Expression+Regulation%2C+Neoplastic%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Gene+Expression+Regulation%2C+Neoplastic) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42859938/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.n
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