KIF11 Might be a Novel Biomarker for Bone Metastasis of Prostate Adenocarcinoma

Abstract

Background: A serious issue derived from Prostate adenocarcinoma (PCa) is its propensity to metastasize to bone, which occurred in up to 90% of patients with advanced PCa. The kinesin superfamily (KIFs) is well-documented oncogenic protein implicated mainly in chromosomal and spindle movements and are involved in some cellular activities, such as mitosis, transport of vesicles, organelles, and mRNAs. However, the clinical significance and biological roles of KIF in bone metastasis of PCa still need further exploration.Method: We download three datasets from the Gene Expression Omnibus (GEO) data repository. Firstly, we merge the three datasets, and then obtain the gene modules most relevant with clinical traits(morbidity of the bone metastasis of PCa) by “WGCNA” R package. Functional enrichment analysis was performed by the DAVID tool and Metascape. Differentially expressed genes (DEGs) between bone metastasis of PCa and primary PCa tissue samples were identified by “limma” R package. Then we intersect the gene module with DEGs. Protein-protein interaction (PPI) network was constructed by Cytoscape, and hub genes were excavated. Immunohistochemistry (IHC) image was downloaded from The Human Protein Atlas (www.proteinatlas.org) to verify the feasibility of the target molecular marker identified by bioinformatics and statistical analysis.Result:16 gene modules were obtained through WGCNA analysis and the tan module is most related to the occurrence of bone metastasis, containing 147 genes. Thus, we selected the tan module for further analysis. 877 DEGs were detected by limma package of R software. After taking the intersection of the DEGs and tan module, we got 51 common genes. Protein-protein interaction network (PPI) was constructed for the 51 genes. 7 hub genes (BUB1, KIF2C, RACGAP1, CENPE, KIF11, TTK, KIF20A) were identified from the common results of four different algorithms (Betweenness, Closeness, EcCentricity, and Radiality). Survival analysis based on disease free survival (DFS) was carried out for the 7 hub genes, and all of them have significant poor prognostic performance (P<0.05). And the bubble charts were plotted for functional annotation of the miRNA which can be the regulating factors of the hub genes. Univariate and multivariate logistic regression analysis were performed for screening the independent risk factors of the bone metastasis of PCa, and KIF11 was finally obtained. The immunohistochemical image of bone metastasis of PCa was obtained on the protein Atlas, which showed a strong positive expression of KIF11.Conclusion: In current study, molecules strongly correlated with the occurrence of bone metastasis of PCa were excavated. And provide the evidence that KIF11 may serve as a potential bone metastasis marker in PCa, which might be used for the guidance of clinical practice.