ArticleFrontiers in immunology2023
Identification and validation of a novel cuproptosis-related stemness signature to predict prognosis and immune landscape in lung adenocarcinoma by integrating single-cell and bulk RNA-sequencing.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 15 citations in OpenAlex.
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Machine learning-based model identifies a novel cuproptosis-related mitochondrial gene signature with a key role in the prognosis and treatment of lung adenocarcinoma.Oncology letters · 2025Article
- Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance.Molecular cancer · 2025Review
- Senescent fibroblasts secrete CTHRC1 to promote cancer stemness in hepatocellular carcinoma.Cell communication and signaling : CCS · 2025Article
- Ferroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer.Journal of gastroenterology · 2025Article
- Tumor heterogeneity assessment using single-cell RNA sequencing (scRNA-seq): applications in lung cancer for diagnosis and treatment.Frontiers in immunology · 2025Review
- Review
- Unveiling the unique role of TSPAN7 across tumors: a pan-cancer study incorporating retrospective clinical research and bioinformatic analysis.Biology direct · 2024Article
- Mechanisms of cuproptosis and its relevance to distinct diseases.Apoptosis : an international journal on programmed cell death · 2024Review
- Cuproptosis, the novel type of oxidation-induced cell death in thoracic cancers: can it enhance the success of immunotherapy?Cell communication and signaling : CCS · 2024Review
- The role of collagen triple helix repeat containing 1 (CTHRC1) in cancer development and progression.Expert opinion on therapeutic targets · 2024Review
- Construction of a prognostic model based on memory CD4+ T cell-associated genes for lung adenocarcinoma and its applications in immunotherapy.CPT: pharmacometrics & systems pharmacology · 2024Article
- Commentary: Copper and cuproptosis-related genes in hepatocellular carcinoma: therapeutic biomarkers targeting tumor immune microenvironment and immune checkpoints.Frontiers in immunology · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Cancer stem cells (CSCs) play vital roles in lung adenocarcinoma (LUAD) recurrence, metastasis, and drug resistance. Cuproptosis has provided a novel insight into the treatment of lung CSCs. However, there is a lack of knowledge regarding the cuproptosis-related genes combined with the stemness signature and their roles in the prognosis and immune landscape of LUAD. Methods: Cuproptosis-related stemness genes (CRSGs) were identified by integrating single-cell and bulk RNA-sequencing data in LUAD patients. Subsequently, cuproptosis-related stemness subtypes were classified using consensus clustering analysis, and a prognostic signature was constructed by univariate and least absolute shrinkage operator (LASSO) Cox regression. The association between signature with immune infiltration, immunotherapy, and stemness features was also investigated. Finally, the expression of CRSGs and the functional roles of target gene were validated Results: We identified six CRSGs that were mainly expressed in epithelial and myeloid cells. Three distinct cuproptosis-related stemness subtypes were identified and associated with the immune infiltration and immunotherapy response. Furthermore, a prognostic signature was constructed to predict the overall survival (OS) of LUAD patients based on eight differently expressed genes (DEGs) with cuproptosis-related stemness signature (KLF4, SCGB3A1, COL1A1, SPP1, C4BPA, TSPAN7, CAV2, and CTHRC1) and confirmed in validation cohorts. We also developed an accurate nomogram to improve clinical applicability. Patients in the high-risk group showed worse OS with lower levels of immune cell infiltration and higher stemness features. Ultimately, further cellular experiments were performed to verify the expression of CRSGs and prognostic DEGs and demonstrate that SPP1 could affect the proliferation, migration, and stemness of LUAD cells. Conclusion: This study developed a novel cuproptosis-related stemness signature that can be used to predict the prognosis and immune landscape of LUAD patients, and provided potential therapeutic targets for lung CSCs in the future.
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