This study aimed to look at how long noncoding RNA’s (lncRNAs) are related to immune molecular classification and its clinical outcomes in terms of cancer immunotherapy. It is known that lncRNAs play a role in both the innate and adaptive immunity within cancer. The lncRNAs intervene and assist the functional of immunologic cells, their pathways, and their genes. While previous studies have looked at the interactions between a lncRNAs biology and immune microenvironment components, this study is the first, to their knowledge, to identify lncRNA-based immune subtypes that are linked to a response to clinical cancer immunotherapy.
An individual patient-level analysis was conducted on 3,370 patients between June and September in 2019 that used proven lncRNA and genomic data. From the analysis, a pan-cancer multicohort study consisted of 406 patients receiving immunotherapy for bladder cancer, 457 for melanoma, 513 for lung cancer, and 1,082 for breast cancer. The endpoints for this study was the overall survival of the patient and both the objective response rate and disease control rate. An R package clusterProfiler (an analysis module that “automates the process of biological-term classification and the enrichment of the analysis of gene clusters” [ncbi reference]) was used for gene ontology. Along with the R package clusterProfile, many other R packages were used to calculate gene set variation analysis (GSVA) enrichment scores, assess differences between GSVA enrichment scores and different lncRNA classes, and numerically estimate and rank the importance of lncRNAs.
A few discoveries were made as results were collected. First, two distinct lncRNA-based classes (immune functional and immune nonfunctional) were linked to significantly different overall survival rates. The immune functional class showed a higher probability of overall survival by about 15%-20%. The graph comparing this finding as well as the overall survival when comparing the nuclear factor-kB-interacting lncRNA (NKILA) is shown below. It was also found that patients who had lived longer experienced a reduced expression of immune cells, immune checkpoints, and human leukocyte antigen levels; the opposite was found for those that did not survive as long. As for the NKILA levels in the graph below, shows that low NKILA levels showed greater survivability. Four specific NKILAs were found to be especially important. These NKILAs were then further investigated how each of them compares against each other while still looking at overall survivability. The graph showing these comparisons is located on the top right-hand side of the following page.