Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer

SIMPLE SUMMARY: Lung cancer (LC) is the tumor with the highest global mortality rate. Novel personalized therapies are currently being tested (e.g., targeted inhibitors, the immune-checkpoint inhibitors), but they cannot yet prevent the very frequent relapse and generalized metastases observed in a large population of LC patients. Currently, there is an urgent need for novel reliable biomarkers for the prognosis and diagnosis of LC. Through the systematic analysis of multiple deposited expression datasets, this report aims to explore the role of the Yin-Yang 1 (YY1) transcription factor and its target the Raf Kinase Inhibitory Protein (RKIP) in LC. The computational analysis suggested the predictive diagnostic and prognostic roles for both YY1 and RKIP stimulating further studies for proving their implication as novel biomarkers, as well as therapeutically druggable targets in LC. ABSTRACT: Lung cancer (LC) represents a global threat, being the tumor with the highest mortality rate. Despite the introduction of novel therapies (e.g., targeted inhibitors, immune-checkpoint inhibitors), relapses are still very frequent. Accordingly, there is an urgent need for reliable predictive biomarkers and therapeutically druggable targets. Yin-Yang 1 (YY1) is a transcription factor that may work either as an oncogene or a tumor suppressor, depending on the genotype and the phenotype of the tumor. The Raf Kinase Inhibitory Protein (RKIP), is a tumor suppressor and immune enhancer often found downregulated in the majority of the examined cancers. In the present report, the role of both YY1 and RKIP in LC is thoroughly explored through the analysis of several deposited RNA and protein expression datasets. The computational analyses revealed that YY1 negatively regulates RKIP expression in LC, as corroborated by the deposited YY1-ChIP-Seq experiments and validated by their robust negative correlation. Additionally, YY1 expression is significantly higher in LC samples compared to normal matching ones, whereas RKIP expression is lower in LC and high in normal matching tissues. These observed differences, unlike many current biomarkers, bear a diagnostic significance, as proven by the ROC analyses. Finally, the survival data support the notion that both YY1 and RKIP might represent strong prognostic biomarkers. Overall, the reported findings indicate that YY1 and RKIP expression levels may play a role in LC as potential biomarkers and therapeutic targets. However, further studies will be necessary to validate the in silico results.