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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Transcript-Level Expression Patterns of Necroptosis-Related Genes RIPK1, RIPK3, and MLKL in Surgically Resected Non-Small Cell Lung Cancer: An Exploratory Single-Center Study

6 affiliations
  1. 1Department of Thoracic Surgery, Faculty of Medicine, Dokuz Eylül University, 35330Izmir, Türkiye
  2. 2Department of Medical Oncology, Oncology Institute, Dokuz Eylül University, 35330 Izmir, Türkiye
  3. 3Department of Basic Oncology, Oncology Institute, Dokuz Eylül University, 35330 Izmir, Türkiye
  4. 4Department of Respiratory Disease, Faculty of Medicine, Dokuz Eylül University, 35330 Izmir, Türkiye
  5. 5Department of Pathology, Faculty of Medicine, Dokuz Eylül University, 35330 Izmir, Türkiye
  6. 6Department of Biostatistics and Medical Informatics, Faculty of Medicine, Dokuz Eylül University, 35330 Izmir, Türkiye

Abstract

Necroptosis is a regulated inflammatory form of programmed cell death mediated by RIPK1, RIPK3, and MLKL, but its clinical relevance in surgically resected non-small cell lung cancer (NSCLC) remains uncertain. This study evaluated the transcript-level expression of these genes and their associations with survival in 41 patients who underwent complete NSCLC resection without preoperative therapy. RNA was isolated from frozen tumor tissues, and mRNA expression was quantified using RT-qPCR. Expression was analyzed primarily as continuous log2(expression + 1)-transformed variables in Cox proportional hazards models; median-based groups were used only for exploratory Kaplan–Meier visualization. The cohort comprised 34 males and 7 females, with a mean age of 61.0 years; 41.5% had adenocarcinoma and 58.5% had squamous cell carcinoma. The maximum follow-up was 145 months, and the 5-year overall survival rate was 46.3%. None of the three genes was significantly associated with overall or disease-free survival in either univariable or restricted adjusted Cox models. Median-based analyses similarly showed no significant survival differences. These findings do not support RIPK1, RIPK3, or MLKL transcript levels as standalone prognostic biomarkers in surgically resected NSCLC. Larger studies integrating transcriptomic, protein-level, and functional assessments are warranted.

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BibTeX
@article{ulugun2026transcriptlevel,
  title = {{Transcript-Level Expression Patterns of Necroptosis-Related Genes RIPK1, RIPK3, and MLKL in Surgically Resected Non-Small Cell Lung Cancer: An Exploratory Single-Center Study}},
  author = {Fatma Ilknur Ulugun and Tuğba Yavuzşen and Safiye Aktaş and Zekiye Sultan Altun and Nezih Özdemir and Gökçen Ömeroğlu Şimşek and Duygu Gürel and Burçin Baran and Mehmet Emin Arayici},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = sep,
  doi = {10.3390/ijms27188361},
  url = {https://www.mdpi.com/1422-0067/27/18/8361},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Transcript-Level Expression Patterns of Necroptosis-Related Genes RIPK1, RIPK3, and MLKL in Surgically Resected Non-Small Cell Lung Cancer: An Exploratory Single-Center Study
AU  - Fatma Ilknur Ulugun
AU  - Tuğba Yavuzşen
AU  - Safiye Aktaş
AU  - Zekiye Sultan Altun
AU  - Nezih Özdemir
AU  - Gökçen Ömeroğlu Şimşek
AU  - Duygu Gürel
AU  - Burçin Baran
AU  - Mehmet Emin Arayici
PY  - 2026
DA  - 2026/09/19
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27188361
UR  - https://www.mdpi.com/1422-0067/27/18/8361
AB  - Necroptosis is a regulated inflammatory form of programmed cell death mediated by RIPK1, RIPK3, and MLKL, but its clinical relevance in surgically resected non-small cell lung cancer (NSCLC) remains uncertain. This study evaluated the transcript-level expression of these genes and their associations with survival in 41 patients who underwent complete NSCLC resection without preoperative therapy. RNA was isolated from frozen tumor tissues, and mRNA expression was quantified using RT-qPCR. Expression was analyzed primarily as continuous log2(expression + 1)-transformed variables in Cox proportional hazards models; median-based groups were used only for exploratory Kaplan–Meier visualization. The cohort comprised 34 males and 7 females, with a mean age of 61.0 years; 41.5% had adenocarcinoma and 58.5% had squamous cell carcinoma. The maximum follow-up was 145 months, and the 5-year overall survival rate was 46.3%. None of the three genes was significantly associated with overall or disease-free survival in either univariable or restricted adjusted Cox models. Median-based analyses similarly showed no significant survival differences. These findings do not support RIPK1, RIPK3, or MLKL transcript levels as standalone prognostic biomarkers in surgically resected NSCLC. Larger studies integrating transcriptomic, protein-level, and functional assessments are warranted.
SN  - 1422-0067
ER  -