Construction of an Immunogenic Cell Death-Related LncRNA Signature to Predict the Prognosis of Patients with Lung Adenocarcinoma

Abstract Background LUAD is one of the most common malignancies worldwide. This study aimed to construct an immunogenic cell death (ICD)-related long non-coding RNA (lncRNA) signature to effectively predict the prognosis of LUAD patients. Methods The RNA-sequencing and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression analysis was performed to screen the ICD-related lncRNAs associated with prognosis. Then, least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox proportional hazard regression analysis were utilized to construct an ICD-related lncRNA signature. The reliability of the signature was evaluated in the training, validation and whole cohorts. In addition, the differences in the immune landscape and drug sensitivity between the low-risk and high-risk groups were analyzed. Finally, reverse transcription quantitative PCR (RT-qPCR) was used to detect the expression level of the selected ICD-related lncRNAs in cell lines. Results A signature consisting of 5 ICD-related lncRNAs was constructed. Kaplan-Meier (K-M) survival analysis showed that the overall survival (OS) of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The receiver operating characteristic (ROC) curves showed that the signature had good predictive ability. Multivariate Cox regression analysis revealed that the signature was an independent prognostic factor in LUAD. Moreover, the high-risk group had a lower level of antitumor immunity and was less sensitive to some chemotherapeutics and targeted drugs. Finally, the expression level of the selected ICD-related lncRNAs was validated in cell lines by qPCR. Conclusions In this study, an ICD-related lncRNA signature was constructed, which could accurately predict the prognosis of LUAD patients and guide clinical treatment.