Abstract
Growing evidence has demonstrated the functional relevance of long intergenic noncoding RNAs (lincRNAs) to tumorigenesis and immune response. However, immune-related lincRNAs and their value in predicting the clinical outcomes of patients with liver cancer remain largely unexplored. Herein, we utilized the strategy of iterative gene pairing to construct a tumor-specific immune-related lincRNA pairs signature (IRLPS), which did not require specific expression levels, as an indicator of patient outcomes. The 18-IRLPS we developed was associated with overall survival, tumor progression, and recurrence in liver cancer patients. Multivariate analysis revealed that the risk model was an independent predictive factor. A high IRLPS risk was correlated suppressive immune microenvironment, and IRLPS-high patients might benefit more from CD276 blockade or TMIGD2 agonist. Patients in the high-risk group were associated with elevated tumor mutation, increased sensitivity to dopamine receptor antagonists, cisplatin, doxorubicin, and mitomycin but more resistance to vinblastine. Mechanistically, IRLPS high scores might lead to poor prognosis by promoting cell proliferation and metabolic reprogramming. The prognostic significance of the 18-IRLPS was confirmed in independent cancer datasets. These findings highlighted the robust predictive performances of the 18-IRLPS for prognosis and personalized treatment.
Highlights
Growing evidence has demonstrated the functional relevance of long intergenic noncoding RNAs to tumorigenesis and immune response
We retrieved the transcriptome profiles of The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and separated the data of Long noncoding RNAs (lncRNAs) and mRNA using the GENCODE annotation file
18 lincRNA pairs were included in the immunerelated lincRNA pairs signature (IRLPS) using a stepwise method with a multivariate Cox proportional hazards model for overall survival (Fig. 1B)
Summary
Growing evidence has demonstrated the functional relevance of long intergenic noncoding RNAs (lincRNAs) to tumorigenesis and immune response. Immune-related lincRNAs and their value in predicting the clinical outcomes of patients with liver cancer remain largely unexplored. There is growing evidence that immune-related lncRNAs may be novel disease biomolecules for clinical cancer treatment and possess valuable prognostic significance for s urvival[16,17]. We were inspired by the strategy of gene pairing and aimed to discover an immune-related intergenic lncRNAs (lincRNAs)-based risk model for predicting clinically relevant outcomes in patients with HCC. By iteratively comparing the relative expression of tumor-specific immune-associated lincRNA pairs in each sample, we developed a valid signature with no requirement of specific expression levels. We estimated its predictive value among patients with HCC for prognostic effectiveness, tumor immune infiltration, and therapeutic liability in immunotherapy, targeted therapy, and chemotherapy. We validated its predictive efficacy in multiple cancer types
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
