Integrated Bioinformatics and Experimental Validation to Identify a Disulfidptosis-Related lncRNA Model for Prognostic Prediction in Papillary Renal Cell Carcinoma

Aims: This study aimed to construct a prognostic model for papillary renal cell carcinoma (pRCC) utilizing disulfidptosis-associated long non-coding RNAs (lncRNAs). Additionally, it investigated the potential of these lncRNAs in predicting immune responses and drug sensitivity in pRCC. Background LncRNAs have been implicated in the progression and prognosis of pRCC. Recently, disulfidptosis, an emerging form of regulated cell death, has shown potential as a therapeutic approach for cancer. However, the potential association between disulfidptosis-related lncRNAs and pRCC remains unclear. Methods: We analyzed transcriptome profiling and clinical data of pRCC patients from The Cancer Genome Atlas database. Using Pearson correlation analysis, we identified lncRNAs associated with disulfidptosis. Based on the identified disulfidptosis-related lncRNAs that were correlated with overall survival (OS), we constructed a novel prediction model using the least absolute shrinkage and selection operator, univariable Cox regression, and multivariable Cox regression analyses. The model's utility was assessed through Kaplan-Meier survival, receiver operating characteristics, and principal component analyses. Moreover, functional analysis helped identify potential prognostic mechanisms, and the prediction of chemical drugs for pRCC was also performed. Finally, qRT-PCR validated the expression of prognostic lncRNAs in pRCC cells and patient samples. Results: Our prediction model was based on nine disulfidptosis-related lncRNAs. Evaluation and validation analyses demonstrated that the model had excellent, consistent, and independent prognostic value for pRCC patients, with area under the curve (AUC) values of 0.954, 0.910, and 0.830 for 1-, 3-, and 5-year OS, respectively. Through functional analysis, we discovered a significant correlation between the identified prognostic signature and immunity. Additionally, in terms of chemotherapy sensitivity, our analysis indicated that the low-risk group exhibited higher sensitivity to sunitinib and pazopanib. Furthermore, the expression patterns of the identified lncRNAs were validated in samples obtained from pRCC cells and patients. Conclusion: This study successfully established and validated a novel disulfidptosis-related prediction model. The findings suggest the potential involvement of immune-related pathways in lncRNA signature-associated survival. This model holds promise for differentiating prognosis and improving personalized therapeutic strategies for pRCC in clinical practice.