NAD‐Associated lncRNA Prognostic Model for ccRCC Survival and Immunotherapy Response

Background Clear cell renal cell carcinoma (ccRCC) is one of the most common primary malignancies of the urinary system, characterized by high heterogeneity and complex immune evasion mechanisms. Despite the availability of treatments such as surgery, chemotherapy, and immunotherapy, their efficacy remains limited, and predicting therapeutic response continues to be challenging. NAD + metabolism is known to play a key role in cancer development, progression, and immune evasion. Additionally, long noncoding RNAs (lncRNAs) are critical regulators of the tumor immune microenvironment. This study aimed to explore the prognostic role of NAD + ‐associated lncRNAs in ccRCC and their relationship with immunotherapy response. Methods Using integrated gene expression data from ccRCC patients, we constructed a prognostic model based on NAD + ‐associated lncRNAs. First, we identified relevant lncRNAs and validated their differential expression and clinical relevance in ccRCC through bioinformatics analyses. Next, we developed a prognostic model using Cox regression analysis and assessed its ability to predict patient outcomes, characterize the tumor immune microenvironment, and evaluate sensitivity to immunotherapy. Results A total of 10 NAD + ‐associated lncRNAs were identified, exhibiting significant differential expression and strong correlations with patient survival. The prognostic model constructed using Cox regression analysis showed high predictive accuracy (1‐year survival AUC: 0.778) and effectively assessed the tumor immune microenvironment and sensitivity to immunotherapy. This model revealed that NAD + ‐associated lncRNAs are not only independent prognostic factors but also potential indicators of poor immunotherapy response in high‐risk patients.