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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Transcript-Level Expression Patterns of Necroptosis-Related Genes RIPK1, RIPK3, and MLKL in Surgically Resected
Fatma Ilknur Ulugun1, Tuğba Yavuzşen2, Safiye Aktaş3
1Department of Thoracic Surgery, Faculty of Medicine, Dokuz Eylül University, 35330Izmir, 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.