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Peer-reviewedCC BY-NC 4.0The Journal of International Medical Research

Identification of a necroptosis-related lncRNA prognostic signature and the hub RBP HNRNPK in esophageal squamous cell carcinoma

  • Shaoyi Zheng1,2
  • Haoshuai Yang2,3
  • Wei Liu2
  • Feihang Zhi2
  • Honghe Luo2
  • Yanfen Feng4
  • Yiyan Lei2
4 affiliations
  1. 1Institute of Chest Wall Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China
  2. 2Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  3. 3Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, China
  4. 4State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{zheng2026identification,
  title = {{Identification of a necroptosis-related lncRNA prognostic signature and the hub RBP HNRNPK in esophageal squamous cell carcinoma}},
  author = {Shaoyi Zheng and Haoshuai Yang and Wei Liu and Feihang Zhi and Honghe Luo and Yanfen Feng and Yiyan Lei},
  journal = {The Journal of International Medical Research},
  year = {2026},
  month = sep,
  doi = {10.1177/03000605261486721},
  url = {https://doi.org/10.1177/03000605261486721},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Identification of a necroptosis-related lncRNA prognostic signature and the hub RBP HNRNPK in esophageal squamous cell carcinoma
AU  - Shaoyi Zheng
AU  - Haoshuai Yang
AU  - Wei Liu
AU  - Feihang Zhi
AU  - Honghe Luo
AU  - Yanfen Feng
AU  - Yiyan Lei
PY  - 2026
DA  - 2026/09/17
JO  - The Journal of International Medical Research
DO  - 10.1177/03000605261486721
UR  - https://doi.org/10.1177/03000605261486721
AB  - 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.
SN  - 0300-0605
SN  - 1473-2300
ER  -