Single-cell and bulk RNA-sequence identify an immune-derived lncRNA-mRNA signature for predicting clinical outcomes and immunotherapeutic response of prostate cancer.

Immunotherapy has limited effectiveness in prostate cancer (PCa), often classified as a "cold tumor" due to immune-related long non-coding RNAs (lncRNAs) and mRNAs. We developed and validated a consensus immune-related lncRNA and mRNA signature (ILMS) to enhance immunotherapy efficacy for PCa patients. By analyzing seven independent datasets, including our own, we confirmed that ILMS is a robust predictor of biochemical recurrence (BCR). Compared to 70 other published signatures, ILMS showed the highest ability to anticipate PCa prognosis. Single-cell analysis indicated that ILMS-high patients had abundant immune cell infiltration, suggesting a favorable response to immunotherapy. Additionally, ILMS was positively associated with immune checkpoints LAG3, TIM3, and TIGIT, identifying patients likely to benefit from immunotherapy. This model will be further validated and refined in subsequent studies.