Vivarelli Silvia, Falzone Luca, Grillo Caterina Maria, Bonavida Benjamin, Crimi Claudia, La Mantia Ignazio, Libra Massimo
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Epidemiology and Biostatistics Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", 80131 Naples, Italy.
Cancers (Basel). 2022 Feb 12;14(4):922. doi: 10.3390/cancers14040922.
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 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.
肺癌（LC）是一种全球性威胁，是死亡率最高的肿瘤。尽管引入了新型疗法（如靶向抑制剂、免疫检查点抑制剂），但复发仍然非常频繁。因此，迫切需要可靠的预测性生物标志物和可用于治疗的药物靶点。阴阳1（YY1）是一种转录因子，根据肿瘤的基因型和表型，它既可以作为癌基因发挥作用，也可以作为肿瘤抑制因子发挥作用。Raf激酶抑制蛋白（RKIP）是一种肿瘤抑制因子和免疫增强剂，在大多数检测的癌症中常被发现表达下调。在本报告中，通过分析几个已存档的RNA和蛋白质表达数据集，深入探讨了YY1和RKIP在肺癌中的作用。计算分析表明，YY1在肺癌中负调控表达，这一点得到了存档的YY1-ChIP-Seq实验的证实，并通过它们之间强烈的负相关得到验证。此外，与正常匹配样本相比，肺癌样本中YY1的表达显著更高，而RKIP在肺癌中的表达较低，在正常匹配组织中表达较高。与许多当前的生物标志物不同，这些观察到的差异具有诊断意义，ROC分析证明了这一点。最后，生存数据支持YY1和RKIP都可能代表强大的预后生物标志物这一观点。总体而言，报告结果表明，YY1和RKIP的表达水平可能作为潜在的生物标志物和治疗靶点在肺癌中发挥作用。然而，需要进一步的研究来验证计算机模拟结果。
