Frontiers in Genetics (Sep 2022)
Identification of a lncRNA based signature for pancreatic cancer survival to predict immune landscape and potential therapeutic drugs
Abstract
Pancreatic cancer is one major digestive malignancy with a poor prognosis. Given the clinical importance of lncRNAs, developing a novel molecular panel with lncRNAs for pancreatic cancer has great potential. As a result, an 8-lncRNA-based robust prognostic signature was constructed using a random survival forest model after examing the expression profile and prognostic significance of lncRNAs in the PAAD cohort from TCGA. The efficacy and effectiveness of the lncRNA-based signature were thoroughly assessed. Patients with high- and low-risk defined by the signature underwent significantly distinct OS expectancy. Most crucially the training group’s AUCs of ROC approached 0.90 and the testing group similarly had the AUCs above 0.86. The lncRNA-based signature was shown to behave as a prognostic indicator of pancreatic cancer, either alone or simultaneously with other factors, after combined analysis with other clinical-pathological factors in Cox regression and nomogram. Additionally, using GSEA and CIBERSORT scoring methods, the immune landscape and variations in biological processes between high- and low-risk subgroups were investigated. Last but not least, drug databases were searched for prospective therapeutic molecules targeting high-risk patients. The most promising compound were Afatinib, LY-303511, and RO-90-7501 as a result. In conclusion, we developed a novel lncRNA based prognostic signature with high efficacy to stratify high-risk pancreatic cancer patients and screened prospective responsive drugs for targeting strategy.
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