Bioinformatic and Experimental Analyses Reveal That KIF4A Is a Biomarker of Therapeutic Sensitivity and Predicts Prognosis in Cervical Cancer Patients

Objective This study aims to investigate the expression,prognostic value,and function of kinesin superfamily 4A(KIF4A)in cervical cancer.Methods Cervical cancer cell lines(Hela and SiHa)and TCGA data were used for experimental and bioinformatic analyses.Overall survival(OS)and progression free survival(PFS)were compared between patients with high or low KIF4A expression.Copy number variation(CNV)and somatic mutations of patients were visualized and GISTIC 2.0 was used to identify significantly altered sites.The function of KIF4A was also explored based on transcriptome analysis and validated by experimental methods.Chemotherapeutic and immunotherapeutic benefits were inferred using multiple reference databases and algorithms.Results Patients with high KIF4A expression had better OS and PFS.KIF4A could inhibit proliferation and migration and induce G1 arrest of cervical cancer cells.Higher CNV load was observed in patients with low KIF4A expression,while the group with low KIF4A expression displayed more significantly altered sites.A total of 13 genes were found to mutate more in the low KIF4A expression group,including NOTCH1 and PUM1.The analysis revealed that low KIF4A expression may indicate an immune escape phenotype,and patients in this group may benefit more from immunotherapy.With respect to chemotherapy,cisplatin and gemcitabine may respond better in patients with high KIF4A expression,while 5-fluorouracil etc.may be responded better in patients with low KIF4A expression Conclusion KIF4A is a tumor suppressor gene in cervical cancer,and it can be used as a prognostic and therapeutic biomarker in cervical cancer.

Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways

Background:Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms.Methods:Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogenactivated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests. Results:The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree ( χ2 = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways. Conclusions:KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.