Journal of International Medical Research · Published 2026-09-17 · Journal article · DOI 10.1177/03000605261486721
Shaoyi Zheng, Haoshuai Yang, Wei Liu, Feihang Zhi, Honghe Luo, Yanfen Feng, Yiyan Lei
Objective Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with poor prognosis. Necroptosis is important for tumor immunity, but its role in ESCC remains unclear. This retrospective bioinformatics study aimed to investigate the prognostic value of necroptosis-related long non-coding RNAs (lncRNAs) and to identify key lncRNA-binding proteins (RBPs) in ESCC patients. Methods RNA transcriptome and clinical data of ESCC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Necroptosis-related lncRNAs were identified through correlation analysis with necroptosis-related genes, subjected to consensus cluster analysis, and used to construct a prognostic risk model via least absolute shrinkage and selection operator (LASSO) regression. The hub RBP was experimentally validated by quantitative polymerase chain reaction (qPCR) using 30 pairs of ESCC and adjacent normal tissues from patients who underwent surgical resection. Results A total of 30 necroptosis-related lncRNAs were significantly correlated with overall survival (OS). The upregulated lncRNAs in the risk model were associated with high immune scores, innate immune cell infiltration, cluster 2 classification, and advanced T-stage disease ( p < 0.05). Three hub RBPs (HNRNPA1, HNRNPC, and HNRNPK) were identified through protein-protein interaction network analysis. qPCR confirmed that HNRNPK was significantly overexpressed in ESCC tissues compared to adjacent normal tissues ( p < 0.05). Conclusions The necroptosis-related lncRNA risk model is an independent prognostic factor for ESCC patients. HNRNPK was identified as a hub RBP significantly overexpressed in ESCC tissues. We hypothesize that HNRNPK may promote tumor progression through regulating proto-oncogene expression or modulating the immune microenvironment, though this requires further mechanistic validation.
Abstract from DOAJ. Public domain (CC0 1.0).
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Zheng, S., Yang, H., Liu, W., et al. (2026). Identification of a necroptosis-related lncRNA prognostic signature and the hub RBP HNRNPK in esophageal squamous cell carcinoma. Journal of International Medical Research. https://doi.org/10.1177/03000605261486721