Prognostic Implications of PPL Expression in Ovarian Cancer

Periplakin (PPL) is a main member in plakin family, which plays important role in cellular adhesion complexes supporting and cytoskeletal integrity supplying. PPL was reported to be a potential biomarker candidate for several types of cancers. However, the biological functions and underlying mechanisms of PPL in ovarian cancer (OV) remain unclear. In the present study, we used GEPIA2, Human Protein Atlas, Oncomine, LinkedOmics, Kaplan-Meier Plotter, String, CytoHubba plug-in and TIMER to determine the associations among PPL expression, prognosis, and immune cell infiltration in OV. RT-qPCR and IHC analysis were conducted to validated the role of PPL in an independent OV cohort. Compared with the ovaries tissues from multiple datasets, levels of PPL mRNA and protein expression were obviously higher in OV tumors(P＜0.05), and a poor survival in OV was found to be strongly correlated with high PPL expression (P<0.05). Moreover, the results were further validated by RT-qPCR and IHC analysis in an independent OV cohort. A gene-clinical nomogram was constructed, including PPL expression and clinical characterization in TCGA. Functional network analysis suggested that PPL regulates important pathways like Wnt signaling pathway, MAPK signaling pathway. Ten hub genes (LAMC2, PXN, LAMA3, LAMB3, LAMA5, ITGA3, TLN1, ACTN4, ACTN1, and ITGB4) were found to be positively associated with PPL. PPL expression was negatively correlated with infiltrating levels of CD4+ T cell macrophages, neutrophils, and dendritic cells. In conclusion, PPL may be an unfavorable prognostic biomarker candidate in OV, which was also correlated with immune infiltrating and might function in immunotherapy response.