Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma.

Abstract

Objective:

Cuproptosis is a newly discovered copper-independent cell death modality, and limited evidence suggests the critical implications in human cancers. Nonetheless, the clinical impacts of cuproptosis-relevant lncRNAs in lung adenocarcinoma (LUAD) remain largely ill-defined. The present study was aimed at defining a cuproptosis-relevant lncRNA signature for LUAD and discuss the clinical utility.

Methods:

We collected transcriptome expression profiling, clinical information, somatic mutation, and copy number variations from TCGA-LUAD cohort retrospectively. The genetic alterations of cuproptosis genes were systematically assessed across LUAD, and cuproptosis-relevant lncRNAs were screened for defining a LASSO prognostic model. Genomic alterations, immunological and stemness features, and therapeutic sensitivity were studied with a series of computational approaches.

Results:

Cuproptosis genes displayed aberrant expression and widespread genomic alterations across LUAD, potentially modulated by m6A/m5C/m1A RNA modification mechanisms. We defined a cuproptosis-relevant lncRNA signature, with a reliable efficacy in predicting clinical outcomes. High-risk subset displayed higher somatic mutations, CNVs, TMB, SNV neoantigens, aneuploidy score, CTA score, homologous recombination defects, and intratumor heterogeneity, cytolytic activity, CD8+ T effector, and antigen processing machinery, proving that this subset might benefit from immunotherapy. Increased stemness indexes and activity of oncogenic pathways might contribute to undesirable prognostic outcomes for high-risk subset. Additionally, high-risk patients generally exhibited higher response to chemotherapeutic agents (cisplatin, etc.). We also predicted several small molecule compounds (GSK461364, KX2-391, etc.) for treating this subset.

Conclusion:

Accordingly, this cuproptosis-relevant lncRNA signature offers an efficient approach to identify and characterize diverse prognosis, genomic alterations, and treatment outcomes in LUAD, thus potentially assisting personalized therapy.

• Authors: Zhuning Wang, Junqiao Yao, Tengyu Dong, Xing Niu
• Journal: Journal of immunology research (J Immunol Res) Vol. 2022 Pg. 2756611 ( 2022) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 36281357 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Zhuning Wang et al.

Chemical References

• Biomarkers, Tumor
• Cisplatin
• Copper
• RNA, Long Noncoding
• tirbanibulin

Topics

• Humans
• Adenocarcinoma (genetics)
• Biomarkers, Tumor (genetics)
• Cisplatin
• Copper
• DNA Copy Number Variations
• Gene Expression Regulation, Neoplastic
• Genomics
• Lung (pathology)
• Lung Neoplasms (drug therapy, genetics)
• Retrospective Studies
• RNA, Long Noncoding (genetics)
• ROC Curve
• Apoptosis