Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments
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Cancer Cell International Open Access
PRIMARY RESEARCH
Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments Lingling Gao1,2, Xiao Li1,2, Qian Guo1,2, Xin Nie1,2, Yingying Hao1,2, Qing Liu1,2, Juanjuan Liu1,2, Liancheng Zhu1,2, Limei Yan1,2 and Bei Lin1,2*
Abstract Background: Plakophilins (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. Methods: The 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. Results: The 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 cytokinemediated 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. Conclusion: Members 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. Keywords: Ovarian cancer, PKP1/2/3, Prognosis, Biomarkers, Immune infiltration, Bioinformatics analysis
*Correspondence: [email protected] 1 Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang 110004, Liaoning, China Full list of author information is available at the end of the article
Background Ovarian cancer (OC) is one of the most common gynecological malignancy in female reproductive system worldwide, which has the characteristics of high metastasis, chemotherapy resistance and recurrence after surgery. Over 70% of the patients are in the advanced stage at age
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