Background: Nasopharyngeal carcinoma (NPC) is a highly invasive malignancy which has unique characteristics when found among individuals from certain ethnic or geographic populations. The role and molecular mechanism of Polo-like kinase 1 (PLK1) in NPC remain yet to be clarified. Hence, the aim of this study is to identify the clinical implications of PLK1 in NPC based on gene chip, tissue microarray, and other silico approaches.
Methods: Relevant data related to PLK1 levels in NPC was screened for by searching in SRA, GEO, ArrayExpress, Oncomine and throughout the existing literature on this topic. The raw data about gene chips were normalized by using an RMA algorithm provided by "Limma" package. Furthermore, the "SVA" package of R software was used to remove the batch effect and data from the same platform were merged into one part. The differential expression levels of PLK1 between NPC and non-NPC tissues were extracted and analyzed with the Student's t-test. Meta-analyses were used to calculate the standard mean difference and sROC. Furthermore, in-house immunohistochemistry was performed with tissue microarrays. Weighted correlation network analysis was used to identify the PLK1-related genes. Several bioinformatic evaluations, including the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interactions, were also performed to assess the PLK1-related pathways.
Results: The tissue microarray and gene chips indicated that the PLK1 levels clearly had an up-regulating trend as compared to the non-cancerous controls. These trends were observed in both the single study and the comprehensive meta-analysis. The area under the sROC curve in the NPC tissues was 0.87, with pooled sensitivity and specificity at 0.950 and 0.710, respectively, based on 393 NPC tissues and 83 non-cancerous controls. A total of 144 genes were identified as co-expressed genes of PLK1 in NPC and were mainly enriched in the "cell cycle" pathway. Among the genes related to the cell cycle, CDK1, CCNA2 and CCNB2 were all closely related to PLK1 expression level.
Conclusions: PLK1 may play a potential oncogenic role in the tumorigenesis and development of NPC. Since several PLK1 inhibitors have been developed, it is believed that the PLK1 inhibitors have great therapeutic potential in clinic applications for NPC patients.
Keywords: Polo-like Kinase 1; RNA-sequencing; gene chip; nasopharyngeal carcinoma; tissue microarrays.