Expression Of NEK7 In Ovarian Epithelial Cancinoma And Its Clinical Significance

Objective: Ovarian cancer has the highest mortality rate among gynecological tumors.While,it has the characteristics of early onset,symptoms could be negligible and this makes the patients loss the best time for treatments.Therefore,it is of great significance to seek sensitive tumor markers.NEK7 is a protein kinase that regulates the cell cycle and belongs to the NIMA-related protein kinase family.The purpose of this study was to analyze the expression of NEK7 in epithelial ovarian tumors,and to explore the relationship between NEK7 expression and clinic pathological parameters as well as the prognosis of patients with ovarian cancer,and to analyze NEK7 in bioinformatic researches.Methods: 1.Using immunohistochemistry(IHC),along with SP method,aims to detect NEK7 expression of 104 cases of ovarian epithelial malignant tumors,15 cases of ovarian epithelial borderline tumors,14 cases of ovarian epithelial benign tumors and 12 cases of normal ovarian tissue.Then use the collected data to further explore whether the expression of NEK7 in ovarian malignant tumors is related to the clinical pathological parameters and the overall survival of ovarian cancer.2.Through The Cancer Genome Atlas(TCGA),GDSC,Gene Mania,CBio Portal database and GSVA,GSEA analysis method "CIBERSORT" R language package,construct a protein interaction network,analyze the mechanism that it participates in regulating the occurrence and development of ovarian cancer with other related genes,and predict the pathway and function of NEK7 in ovarian cancerResults: 1.The expression of NEk7 was mainly localized in the nucleus and cytoplasm of cells.The positive rate of NEK7 expression in epithelial ovarian malignant tissues(77.9%,81/104)was significantly higher than the one in the benign epithelial ovarian tumors(35.7%,5/14),and normal ovarian tissues(16.7%,2/12).Among 104 patients with ovarian malignant tumors,the positive rate of NEK7 expression in FIGO Ⅲ-Ⅳpatients(89.7%,52/58)was higher than that of FIGO Ⅰ-Ⅱ patients(63.0%,29/46)(P<0.05).Cox univariate analysis showed that the expression level of NEK7(P=0.021,HR=3.394,95%CI:1.199-9.068),FIGO stage(P=0.001,HR=3.328,95%CI:1.600-6.923),and lymph node metastasis(P=0.037,HR=1.588,95%CI:1.028-2.451)were related to the prognosis(all P <0.05).Cox multivariate regression model analysis indicated that FIGO stage(P=0.038,HR=2.387,95%CI:1.048-5.437)is closely related to the prognosis(P<0.05).K-M survival analysis also illustrated that the expression of NEK7 and FIGO stage were both crucial factors affecting the poor prognosis(both P <0.05).Therefore,the expression level of NEK7 may be a prognostic indicator for patients with ovarian epithelial malignant tumors.2.Research using bioinformatics database found that NEK7 is also highly expressed in ovarian cancer tissues.The functional enrichment analysis of NEK7 found that NEK7 is mainly involved in protein secretion,complement,apoptosis,Kras signaling pathway,Notch signaling pathway,and p53 signaling pathway.It affects the occurrence and development of tumors.Gene pathway enrichment of NEK7 found that the enrichment of immune-related pathways is mainly.Drug sensitivity analysis found that the level of NEK7 expression may affect the drug sensitivity of patients to paclitaxel and cisplatin(P<0.05),but has no significant effect on doxorubicin and docetaxel.Immune cell infiltration analysis found that eosinophils and gamma delta T cells were positively correlated with NEK7,while memory B cells and regulatory T cells were negatively correlated with NEK7.The c Bioportal database studied the mutations of core genes in ovarian cancer and found that a total of 29 patients had core gene mutations,and the gene mutation ratio was 14%.Gene MANIA uses the first 20co-expressed genes to construct a protein interaction network.NEK9 and NEK7 have physical interactions,NEK6 and NEK7 share protein domains,PIK3C2 A and CCNT2 are related to prediction,and EFR3 A and NEK7 co-expression are related.These analyses can speculate that NEK7 plays an important role in the immune microenvironment.Conclusion: Our study demonstrated that the expression of NEK7 was associated with the poor prognosis of ovarian cancer,it could be used as a potential prognostic biomarker.