A cuproptosis-related lncRNA signature for predicting prognosis and immunotherapy response of lung adenocarcinoma

Hereditas

Research

Lingxue Tang¹  Wen Li¹  Yinlian Cai¹  Senbang Yao¹  Qianqian Zhang¹  Sheng Yu²  Huaidong Cheng³ 

[1] Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, Anhui, China;Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, Anhui, China;Shenzhen Clinical Medical School, Southern Medical University, Shenzhen, Guangdong, China;Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, China;Shenzhen Clinical Medical School, Southern Medical University, Shenzhen, Guangdong, China;Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, China;

关键词: Lung adenocarcinoma;    Non-small cell lung cancer (NSCLC);    Cuproptosis;    LncRNAs;    Prognostic signature;    Immunotherapy response;   

DOI  :  10.1186/s41065-023-00293-w

 received in 2022-12-10, accepted in 2023-07-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCopper-induced cell death (cuproptosis) is a new regulatory cell death mechanism. Long noncoding RNAs (lncRNAs) are related to tumor immunity and metastasis. However, the correlation of cuproptosis-related lncRNAs with the immunotherapy response and prognosis of lung adenocarcinoma (LUAD) patients is not clear.MethodsWe obtained the clinical characteristics and transcriptome data from TCGA-LUAD dataset (containing 539 LUAD and 59 paracancerous tissues). By utilizing LASSO-penalized Cox regression analysis, we identified a prognostic signature composed of cuproptosis-related lncRNAs. This signature was then utilized to segregate patients into two different risk categories based on their respective risk scores. The identification of differentially expressed genes (DEGs) between high- and low-risk groups was carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We evaluated the immunotherapy response by analyzing tumor mutational burden (TMB), immunocyte infiltration and Tumor Immune Dysfunction and Exclusion (TIDE) web application. The "pRRophetic" R package was utilized to conduct further screening of potential therapeutic drugs for their sensitivity.ResultsWe ultimately identified a prognostic risk signature that includes six cuproptosis-related lncRNAs (AP003778.1, AC011611.2, CRNDE, AL162632.3, LY86-AS1, and AC090948.1). Compared with clinical characteristics, the signature was significantly correlated with prognosis following the control of confounding variables (HR = 2.287, 95% CI = 1.648–3.174, p ˂ 0.001), and correctly predicted 1-, 2-, and 3-year overall survival (OS) rates (AUC value = 0.725, 0.715, and 0.662, respectively) in LUAD patients. In terms of prognosis, patients categorized as low risk exhibited more positive results in comparison to those in the high-risk group. The enrichment analysis showed that the two groups had different immune signaling pathways. Immunotherapy may offer a more appropriate treatment option for high-risk patients due to their higher TMB and lower TIDE scores. The higher risk score may demonstrate increased sensitivity to bexarotene, cisplatin, epothilone B, and vinorelbine.ConclusionsBased on cuproptosis-related lncRNAs, we constructed and validated a novel risk signature that may be used to predict immunotherapy efficacy and prognosis in LUAD patients.

【 授权许可】

CC BY   
© The Author(s) 2023

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