Tumor necrosis factor-related lncRNAs predict prognosis and immunotherapy response for patients with lung adenocarcinoma

Journal of Thoracic Disease

article

Jin-Hua Chen¹  Xuan Wu²  Zi-Ming Wang³  Zi-Yang Liu²  Bao-Xia He¹  Wen-Ping Song¹  Wen-Zhou Zhang¹ 

[1] Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Engineering Research Center for Tumor Precision Medicine and Comprehensive Evaluation, Henan Provincial Key Laboratory of Anticancer Drug Research;Department of Respiratory and Critical Care Medicine, Zhengzhou University People’s Hospital;School of Medical Sciences, Henan University

关键词: Lung adenocarcinoma (LUAD);    tumor necrosis factor (TNF);    long non-coding RNAs (lncRNAs);    prognosis;    immunotherapy response;   

DOI  :  10.21037/jtd-23-184

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: Lung adenocarcinoma (LUAD) has become one of the most lethal cancers, for which the recurrence and survival rates remain unfavorable. The tumor necrosis factor (TNF) family is involved in tumorigenesis and tumor progression. Various long non-coding RNAs (lncRNAs) play important roles by mediating the TNF family in cancer. Therefore, this study aimed to construct a TNF-related lncRNA signature to predict prognosis and immunotherapy response in LUAD. Methods: The expression of TNF family members and their related lncRNAs in a total of 500 enrolled LUAD patients was collected from The Cancer Genome Atlas (TCGA). Univariate Cox and the least absolute shrinkage and selection operator (LASSO)-Cox analysis was used to construct a TNF family-related lncRNA prognostic signature. Kaplan-Meier (KM) survival analysis was used to evaluate survival status. The time-dependent area under the receiver operating characteristic (ROC) curve (AUC) values were used to assess the predictive value of the signature to 1-, 2-, and 3-year overall survival (OS). Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to identify the signature-related biological pathways. Furthermore, tumor immune dysfunction and exclusion (TIDE) analysis was employed to evaluate immunotherapy response. Results: A total of 8 TNF-related lncRNAs significantly associated with OS of LUAD patients were used to construct a TNF family-related lncRNA prognostic signature. According to risk score, these patients were divided into high- and low-risk subgroups. The KM survival analysis indicated that patients in the high-risk group showed significantly less favorable OS than that of low-risk group. The AUC values in predicting 1-, 2-, and 3-year OS were 0.740, 0.738, and 0.758, respectively. Moreover, the GO and KEGG pathway analyses demonstrated that these lncRNAs were closely involved in immune-related signaling pathways. The further TIDE analysis indicated that high-risk patients had a lower TIDE score than that of low-risk patients, indicating that high-risk patients may be appropriate candidates for immunotherapy. Conclusions: For the first time, this study constructed and validated a prognostic predictive signature of LUAD patients based on TNF-related lncRNAs, and the signature showed good performance to predict immunotherapy response. Therefore, this signature may provide new strategies for individualized treatment of LUAD patients.

【 授权许可】

Unknown