Prognostic implications of PPL expression in ovarian cancer

Abstract

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 GEPIA 2, 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 normal ovary tissues, the levels of PPL mRNA and protein expression were both obviously higher in OV tumors from multiple datasets (P < 0.05), and a poor survival was observed 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 mRNA expression and clinical factors in TCGA. Functional network analysis suggested that PPL participates in the important pathways like Wnt signaling pathway, MAPK signaling pathway. Ten hub genes (LAMC2, PXN, LAMA3, LAMB3, LAMA5, ITGA3, TLN1, ACTN4, ACTN1, and ITGB4) were identified to be positively associated with PPL. Furthermore, 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 function in immunotherapy response.

Uncovering Novel Features of the Pc Locus in Horn Development from Gene-Edited Holstein Cattle by RNA-Sequencing Analysis

“…These terms contained many differentially expressed genes encoding keratin, such as keratin 4 (KRT4), keratin 15 (KRT15), keratin 17 (KRT17), keratin 19 (KRT19), and keratin 80 (KRT80), all of which showed high expression in WH horn bud tissues and low expression in EH horn bud tissues [ 35 ]. This study also enriched the genes encoding structural proteins that link the desmosomes of keratinocytes and epidermal keratinized envelope of keratinocytes, such as periplakin (PPL), which plays important role in cellular adhesion complexes supporting and cytoskeletal integrity supplying [ 36 ], envoplakin (EVPL), which forms a component of desmosomes and the epidermal cornified envelope [ 37 ], etc. In EH horn bud tissue, low expression of all these genes directly affected the keratinization process of the cells.…”