Integrative Genome-Wide Analysis of Long Noncoding RNAs in Diverse Immune Cell Types of Melanoma Patients

Genome-wide identification and characterization of long noncoding RNAs (lncRNA) in individual immune cell lineages helps us better understand the driving mechanisms behind melanoma and advance personalized patient treatment. To elucidate the transcriptional landscape in diverse immune cell types of peripheral blood cells (PBC) in stage IV melanoma, we used whole transcriptome RNA sequencing to profile lncRNAs in CD4⁺, CD8⁺, and CD14⁺ PBC from 132 patient samples. Our integrative computational approach identified 27,625 expressed lncRNAs, 2,744 of which were novel. Both T cells (i.e., CD4⁺ and CD8⁺ PBC) and monocytes (i.e., CD14⁺ PBC) exhibited differential transcriptional expression profiles between patients with melanoma and healthy subjects. Cis- and trans-level coexpression analysis suggested that lncRNAs are potentially involved in many important immune-related pathways and the programmed cell death receptor 1 checkpoint pathways. We also identified nine gene coexpression modules significantly associated with melanoma status, all of which were significantly enriched for three mRNA translation processes. Age and melanoma traits closely correlated with each other, implying that melanoma contains age-associated immune changes. Our computational prediction analysis suggests that many cis- and trans-regulatory lncRNAs could interact with multiple transcriptional and posttranscriptional regulatory elements in CD4⁺, CD8⁺, and CD14⁺ PBC, respectively. These results provide novel insights into the regulatory mechanisms involving lncRNAs in individual immune cell types in melanoma and can help expedite cell type-specific immunotherapy treatments for such diseases.Significance: These findings elucidate melanoma-associated changes to the noncoding transcriptional landscape of distinct immune cell classes, thus providing cell type-specific guidance to targeted immunotherapy regimens. Cancer Res; 78(15); 4411-23. ©2018 AACR.