Functional, Pharmacogenomic, and Immune Landscapes of Long Non-Coding RNAs in Cancer

Area of Science:

• Oncology
• Genomics
• Bioinformatics

Background:

• Long non-coding RNAs (lncRNAs) are increasingly recognized for their regulatory roles in cancer development and progression.
• Their potential as biomarkers and therapeutic targets necessitates comprehensive analysis across diverse cancer types.

Purpose of the Study:

• To systematically investigate the associations between lncRNAs and targeted therapies, immunotherapies, and clinical outcomes in a large cohort of cancer patients.
• To identify specific lncRNAs that can predict response to cancer treatments and influence immune-related adverse events (irAEs).

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) and real-world datasets for comprehensive analysis of lncRNA expression.
• Integrated data from CancerRxTissue and VAEN to identify lncRNA-drug response associations.
• Correlated lncRNA expression with immune checkpoints, infiltration, immunotherapy response, and irAEs.

Main Results:

• Identified over 53,000 lncRNA-pathway associations and millions of lncRNA-drug response associations.
• Discovered 69 lncRNAs linked to immunotherapy response and 2,611 differentially expressed lncRNAs in relation to objective response rate (ORR).
• Found two lncRNAs associated with irAEs and identified 1,376 lncRNAs differing between low and high irAE risk groups.

Conclusions:

• lncRNAs play significant roles in modulating responses to cancer therapies, including targeted and immunotherapies.
• The identified lncRNAs serve as potential biomarkers for predicting treatment efficacy and managing irAEs.
• The developed web portal, PILNC, provides a valuable resource for exploring lncRNA functions in cancer and facilitating further research.