Abstract
BackgroundPlakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. However, the function and potential mechanism of PKP1/2/3 in ovarian cancer (OC) remains unclear. It’s of great value to explore the expression and prognostic values of PKP1/2/3 and their potential mechanisms, immune infiltration in OC.MethodsThe expression levels, prognostic values and genetic variations of PKP1/2/3 in OC were explored by various bioinformatics tools and databases, and PKP2/3 were selected for further analyzing their regulation network and immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted. Finally, the expression and prognosis of PKP2 were validated by immunohistochemistry.ResultsThe expression level and prognosis of PKP1 showed little significance in ovarian cancer, and the expression of PKP2/3 mRNA and protein were upregulated in OC, showing significant correlations with poor prognosis of OC. Functional enrichment analysis showed that PKP2/3 and their correlated genes were significantly enriched in adaptive immune response, cytokine receptor activity, organization of cell–cell junction and extracellular matrix; KEGG analysis showed that PKP2/3 and their significantly correlated genes were involved in signaling pathways including cytokine-mediated signaling pathway, receptor signaling pathway and pathways in cancer. Moreover, PKP2/3 were correlated with lymphocytes and immunomodulators. We confirmed that high expression of PKP2 was significantly associated with advanced stage, poor differentiation and poor prognosis of OC patients.ConclusionMembers of plakophilins family showed various degrees of abnormal expressions and prognostic values in ovarian cancer. PKP2/3 played crucial roles in tumorigenesis, aggressiveness, malignant biological behavior and immune infiltration of OC, and can be regarded as potential biomarker for early diagnosis and prognosis evaluation in OC.
Highlights
Plakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression
Levels of PKP1/2/3 mRNA in various cancers analyzed by Oncomine database To determine the role of PKP1/2/3 in tumorigenesis and development in ovarian cancer, we detected the levels of PKP1/2/3 mRNA in ovarian cancer tissues and normal tissue by Oncomine database
Prognostic values of PKP1/2/3 in patients with ovarian cancer (OC) by Kaplan–Meier Plotter The prognostic values of PKP1/2/3 in patients with OC were explored by Kaplan–Meier Plotter, and the truncated data were set to overall survival (OS) and progression-free survival (PFS), a total of 1657 and 1436 cases in the database met the standards, respectively
Summary
Plakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. Plakophilins (PKPs) are members of subfamily p120ctn (p120-catenins) of the armadillo protein family, which mainly includes p120ctn (p120ctn, CTNND1), NPRAP/ δ-catenin (CTNND2), ARVCF (armadillo repeat gene deleted in velocardio-facial syndrome), p0071/ plakophilin (PKP4), and plakophilin 1/2/3 (PKP1/2/3), while all members of the p120ctn family have characteristic armadillo repeat sequences (arm-repeats), which are flanked by N-terminal head domain and C-terminal tail domain. These molecules play a crucial role in regulating protein binding, cell junction (desmosome and adhesion junction) and signal transduction [4]. Mutation of PKP1 gene caused a skin fragility syndrome characterized by ectodermal dysplasia and skin fragility [9, 10], mutation of PKP2 gene was closely associated with arrhythmogenic right ventricular cardiomyopathy(ARVC) [11]
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