Machine learning reveals diverse cell death patterns in lung adenocarcinoma prognosis and therapy

Wang, Shun; Wang, Ruohuang; Hu, Dingtao; Zhang, Caoxu; Cao, Peng; Huang, Jie

doi:10.1038/s41698-024-00538-5

Cited by 17 publications

(1 citation statement)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lung cancer remains the principal cause of tumor-associated mortality globally, with non-small cell lung cancer (NSCLC) constituting approximately 85% of all cases. The current therapeutic strategies yield a disconcertingly low 5-year survival rate of less than 15% [ 1 , 2 ]. Standard treatment modalities for NSCLC encompass surgical resection, radiation therapy, chemotherapy, targeted therapy, and immunotherapy [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

Wang,

et al. 2024

Cancer Cell Int

Self Cite

View full text Add to dashboard Cite

Ferroptosis, an iron-dependent regulated cell death mechanism, holds significant promise as a therapeutic strategy in oncology. In the current study, we explored the regulatory effects of epigallocatechin gallate (EGCG), a prominent polyphenol in green tea, on ferroptosis and its potential therapeutic implications for non-small cell lung cancer (NSCLC). Treatment of NSCLC cell lines with varying concentrations of EGCG resulted in a notable suppression of cell proliferation, as evidenced by a reduction in Ki67 immunofluorescence staining. Western blot analyses demonstrated that EGCG treatment led to a decrease in the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while increasing the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4). These molecular changes were accompanied by an increase in intracellular iron, malondialdehyde (MDA), and reactive oxygen species (ROS), alongside ultrastructural alterations characteristic of ferroptosis. Through small RNA sequencing and RT-qPCR, transfer RNA-derived small RNA 13502 (tsRNA-13502) was identified as a significant target of EGCG action, with its expression being upregulated in NSCLC tissues compared to adjacent non-tumorous tissues. EGCG was found to modulate the ferroptosis pathway by downregulating tsRNA-13502 and altering the expression of key ferroptosis regulators (GPX4/SLC7A11 and ACSL4), thereby promoting the accumulation of iron, MDA, and ROS, and ultimately inducing ferroptosis in NSCLC cells. This study elucidates EGCG’s multifaceted mechanisms of action, underscoring the modulation of ferroptosis as a viable therapeutic approach for enhancing NSCLC treatment outcomes.

show abstract

Section: Introductionmentioning

confidence: 99%

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

Wang,

et al. 2024

Cancer Cell Int

Self Cite

View full text Add to dashboard Cite

show abstract

Prediction of clinical prognosis and drug sensitivity in hepatocellular carcinoma through the combination of multiple cell death pathways

Chen,

Zhang,

Meng

et al. 2024

Cell Biology International

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor, highlighting a significant need for reliable predictive models to assess clinical prognosis, disease progression, and drug sensitivity. Recent studies have highlighted the critical role of various programmed cell death pathways, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, NETotic cell death, parthanatos, lysosome‐dependent cell death, autophagy‐dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis, in tumor development. Therefore, by investigating these pathways, we aimed to develop a predictive model for HCC prognosis and drug sensitivity. We analyzed transcriptome, single‐cell transcriptome, genomic, and clinical information using data from the TCGA‐LIHC, GSE14520, GSE45436, and GSE166635 datasets. Machine learning algorithms were used to establish a cell death index (CDI) with seven gene signatures, which was validated across three independent datasets, showing that high CDI correlates with poorer prognosis. Unsupervised clustering revealed three molecular subtypes of HCC with distinct biological processes. Furthermore, a nomogram integrating CDI and clinical information demonstrated good predictive performance. CDI was associated with immune checkpoint genes and tumor microenvironment components using single‐cell transcriptome analysis. Drug sensitivity analysis indicated that patients with high CDI may be resistant to oxaliplatin and cisplatin but sensitive to axitinib and sorafenib. In summary, our model offers a precise prediction of clinical outcomes and drug sensitivity for patients with HCC, providing valuable insights for personalized treatment strategies.

show abstract

Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets

Qian,

Long,

Tan

et al. 2024

MedComm

View full text Add to dashboard Cite

Programmed cell death represents a precisely regulated and active cellular demise, governed by a complex network of specific genes and proteins. The identification of multiple forms of programmed cell death has significantly advanced the understanding of its intricate mechanisms, as demonstrated in recent studies. A thorough grasp of these processes is essential across various biological disciplines and in the study of diseases. Nonetheless, despite notable progress, the exploration of the relationship between programmed cell death and disease, as well as its clinical application, are still in a nascent stage. Therefore, further exploration of programmed cell death and the development of corresponding therapeutic methods and strategies holds substantial potential. Our review provides a detailed examination of the primary mechanisms behind apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Following this, the discussion delves into biological functions and diseases associated dysregulated programmed cell death. Finally, we highlight existing and potential therapeutic targets and strategies focused on cancers and neurodegenerative diseases. This review aims to summarize the latest insights on programmed cell death from mechanisms to diseases and provides a more reliable approach for clinical transformation.

show abstract

Machine learning reveals diverse cell death patterns in lung adenocarcinoma prognosis and therapy

Cited by 17 publications

References 83 publications

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

Epigallocatechin gallate modulates ferroptosis through downregulation of tsRNA-13502 in non-small cell lung cancer

Prediction of clinical prognosis and drug sensitivity in hepatocellular carcinoma through the combination of multiple cell death pathways

Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets

Contact Info

Product

Resources

About