Investigating the role of necroptosis-related lncRNAs in the prognosis and immunotherapy in colon adenocarcinoma patients

Background: Necroptosis-related gene (NRG) expression has been implicated in tumor progression and patient prognosis. However, the prognostic value and biological function of long noncoding RNAs (lncRNAs) involved in necroptosis remain largely unknown in colorectal adenocarcinoma (COAD). This study aimed to identify necroptosis-related lncRNAs associated with COAD prognosis and explore their potential therapeutic implications. Methods: We downloaded the RNA-seq and clinical data of COAD patients from The Cancer Genome Atlas to identify NRG-related lncRNAs using Pearson correlation and differential expression analysis (|log2FC| > 1, FDR < 0.05). A prognostic model was constructed using LASSO and multivariate Cox regression analyses and validated by Kaplan–Meier survival and time-dependent ROC analyses. Consensus clustering was performed to identify molecular subgroups, and RT-qPCR was used to validate lncRNA expression in paired stage I and stage III COAD tissues. Results: We constructed a prognostic signature containing three NRG-related lncRNAs, effectively stratifying COAD patients into high- and low-risk groups. Patients in the high-risk group had significantly poorer overall survival (OS) (HR > 1, P < 0.001). The model showed good predictive performance with a 3-year AUC of 0.702. The infiltration of DC, Macrophage, neutrophils and Treg et al immune cells was distinct between high and low risk groups. Compared to the low-risk group, the value of IC50 of patients in high-risk group was lower. Patient in cluster 2 was found to be more sensitive to nine immunotherapeutic drugs. RT-qPCR confirmed that LINC02381 was significantly upregulated in stage III compared with stage I COAD tissues. Conclusions: We developed a novel NRG-related lncRNA signature that effectively predicts COAD prognosis and identifies patient subgroups potentially sensitive to immunotherapy.