Research Paper Volume 15, Issue 5 pp 1543—1563

Identification and integration analysis of a novel prognostic signature associated with cuproptosis-related ferroptosis genes and relevant lncRNA regulatory axis in lung adenocarcinoma

Tianyue Wang1, *,#, , Xinyu Jiang2, *,#, , Ying Lu1, , Yanmin Ruan1, , Jiamin Wang3, ,

  • 1 The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
  • 2 The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
  • 3 The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
* Equal contribution
# Share first authorship

Received: December 30, 2022       Accepted: February 20, 2023       Published: March 3, 2023
How to Cite

Copyright: © 2023 Wang 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.


Lung adenocarcinoma (LUAD) is a highly prevalent malignancy worldwide, and its clinical prognosis assessment and treatment is a major research direction. Both ferroptosis and cuproptosis are novel forms of cell death and are considered to be important factors involved in cancer progression. To further understand the correlation between the cuproptosis-related ferroptosis genes (CRFGs) and the prognosis of LUAD, we explore the molecular mechanisms related to the development of the disease. We constructed a prognostic signature containing 13 CRFGs, which, after grouping based on risk score, revealed that the LUAD high-risk group exhibited poor prognosis. Nomogram confirmed that it could be an independent risk factor for LUAD, and ROC curves and DCA validated the validity of the model. Further analysis showed that the three prognostic biomarkers (LIFR, CAV1, TFAP2A) were significantly correlated with immunization. Meanwhile, we found that a LINC00324/miR-200c-3p/TFAP2A regulatory axis could be involved in the progression of LUAD. In conclusion, our report reveals that CRFGs are well correlated with LUAD and provide new ideas for the construction of clinical prognostic tools, immunotherapy, and targeted therapy for LUAD.


LUAD: lung adenocarcinoma; CRFGs: cuproptosis-related ferroptosis genes; TCGA: The Cancer Genome Atlas; LASSO: least absolute shrinkage and selection operator; ROC: receiver operating characteristic; DCA: decision curve analysis; TME: Tumor microenvironment; LncRNA: long non-coding RNA; MSI: microsatellite instability; NSCLC: non-small cell lung carcinoma; BAP1: BRCA1-Associated Protein 1; GEO: Gene Expression Omnibus; PPI: protein-protein interaction; DEGs: differentially expressed genes; HR: hazard ratio; CI: confidence interval; OS: overall survival; PFS: progression-free survival; TMB: tumor mutational burden; CXR: chest X-ray; GBE1: glycogen branching enzyme; ICB: immune checkpoint blockade; CeRNA: crosstalk-competing endogenous RNA.