Research Paper Volume 15, Issue 11 pp 4794—4819

Identification of hub necroptosis-related lncRNAs for prognosis prediction of esophageal carcinoma

Zhengdong Luo1, *, , E Ding1, *, , Longchen Yu1, , Wenwu Wang2, , Qining Guo1, , Xinyang Li1, , Yifeng Wang1, , Tingting Li1, , Yi Zhang1, *, , Xin Zhang1, *, ,

  • 1 Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
  • 2 Hangzhou Lin’an District Fourth People’s Hospital, Hangzhou, Zhejiang Province, China
* Equal contribution

Received: February 13, 2023       Accepted: May 17, 2023       Published: June 1, 2023
How to Cite

Copyright: © 2023 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Necroptosis is a newly identified programmed cell death associated with the biological process of various cancers, including esophageal carcinoma (ESCA). Meanwhile, the dysregulation of long non-coding RNAs (lncRNAs) is greatly implicated in ESCA progression and necroptosis regulation. However, the lncRNAs involved in regulating necroptosis in ESCA are still unclear. In this study, we aim to explore the expression profile of necroptosis-related lncRNAs (NRLs), and evaluate their roles in ESCA prognosis and treatment. In the present study, 198 differentially expressed NRLs were identified between the ESCA and adjacent normal tissues through screening the data extracted from the Cancer Genome Atlas (TCGA) database. And, a prognostic panel consisting of 6 NRLs was constructed using the LASSO algorithm and multivariate Cox regression analysis. The ESCA patients with high risks had a markedly reduced survival time and higher mortality prevalence. Moreover, C-index of 6 NRLs-panel was superior to 48 published prognostic models based on lncRNAs or mRNAs for ESCA. There were significant differences between the high-risk and low-risk groups in tumor-related pathways, genetic mutations, and drug sensitivity responses. In vitro analysis revealed that inhibition of PVT1 impeded the proliferation, migration, and colony formation of ESCA cells, increased the expressions of p-RIP1 and p-MLKL and promoted necroptosis. By contrast, PVT1 overexpression resulted in a decrease in necroptotic cell death events, thus promoting tumor progression. Collectively, the established 6-NRLs panel was a promising biomarker for the prognostic prediction of ESCA. Moreover, our current findings provided potential targets for individualized therapy for ESCA patients.


ESCA: esophageal carcinoma; ESCC: esophageal squamous cell carcinoma; lncRNAs: long non-coding RNAs; NRLs: necroptosis-related lncRNAs; NRGs: necroptosis-related genes; DE-NRGs: differentially expressed necroptosis-related genes; DE-NRLs: differentially expressed necroptosis-related lncRNAs; TCGA: the Cancer Genome Atlas; TNF-α: tumor necrosis factor-α; RIPK1: receptor interacting protein-1; RIPK3: receptor-interacting protein kinase 3; MLKL: mixed-lineage kinase domain-like protein; CCRT: concurrent chemoradiotherapy; CeRNA: competing endogenous RNA; LASSO: least absolute shrinkage and selection operator; PCA: principal component analysis; ROC: receiver operating characteristic; C-index: concordance index; TMB: tumor mutational burden; GSEA: gene set enrichment analysis; NRGs: necroptosis-related genes; KEGG: Kyoto Encyclopedia of Genes and Genomes; DE-NRGs: differentially expressed NRGs; OS: the overall survival; PPI: protein-protein interaction; IC50: half-maximal inhibitory concentration; AUCs: the area under ROC curves; TLR: Toll-like receptor; AML: acute myeloid leukemia; LUAD: lung adenocarcinoma.