The kinesin superfamily (KIF) is involved in a variety of normal cellular biological activities, such as cell mitosis and intracellular transport of vesicles and organelles . Overexpression of certain kinesins, such as Eg5, can induce excessive spindle separation, causing uneven distribution of genetic material, thereby forming aneuploid progeny cells, which are involved in cancer invasion and metastasis [25–26]. Downregulation of certain kinesins, such as KIF20B, can cause mitotic arrest or cytokinesis defects, triggering apoptosis through p53 or other signaling pathways [25, 27]. Studies have shown that KIF23, as a member of the kinesin superfamily 6, is highly expressed in gastric cancer and is positively correlated with pTNM stage and poor prognosis. Knocking down KIF23 can inhibit the proliferation of gastric cancer cells . Sun  et al. confirmed that TCF-4 regulates KIF23 expression at the transcriptional level, knocking down KIF23 by CHIP and dual luciferase gene reports, and glioma cells show dual and multinucleated cell bodies, thereby inhibiting tumor cell proliferation . Liu  have shown that KIF23 can promote the proliferation, migration and invasion of human hepatocellular carcinoma cells by activating Akt signal transduction pathway. It is shown that KIF23 plays an important role in the occurrence and development of tumors. The fatality rate of ovarian cancer ranks first among gynecological malignant tumors, and 4/5 of the patients are diagnosed with advanced ovarian cancer . At present, the pathogenesis of ovarian cancer is not clear, and there are few studies on KIF23 in ovarian cancer. Therefore, it is of great significance to explore the relationship between KIF23 and ovarian cancer. Through the joint analysis of Oncomine, GEO and TCGA database, the results showed that KIF23 was highly expressed in ovarian cancer, and the high expression of KIF23 was significantly related to tissue differentiation. The overall survival time of patients with high expression of KIF23 was significantly worse than that of patients with low expression of KIF23. The immunohistochemistry results showed that the high expression of KIF23 was significantly correlated with FIGO stage and tissue differentiation. Whether the high expression of KIF23 is related to FIGO stage is not consistent with the conclusion of bioinformatics analysis. We speculate that it may be related to sample size and ethnic differences. The results of survival analysis showed that the overall survival time of patients with high expression of KIF23 was significantly worse than that of patients with low expression, which was consistent with the conclusion of bioinformatics analysis. Therefore, we speculate that KIF23 can be used as a biomarker to guide the early clinical diagnosis and efficacy detection of ovarian cancer.
It is reported that TP53 mutations exist in more than 50% of the advanced epithelial serous ovarian cancers, and the frequency of TP53 mutations can be as high as 80% when using purified tumor samples for sequence analysis [33–36]. TP53 mutation is involved in the occurrence and development of epithelial serous ovarian cancer . Therefore, we analyze the survival curve of ovarian cancer patients according to the status of TP53 in order to determine which patients can benefit from TP53 gene targeting testing. The results suggest that patients with low expression of KIF23 gene have a better prognosis in TP53 mutant ovarian cancer.
Zhang  study found that the presence of TP53 mutations in ovarian cancer aggravates genomic instability and promotes the expression of MDR1, which in turn activates chemotherapy resistance in ovarian cancer. Murakami H  et al isolated 9 up-regulated genes including KIF23 from paclitaxel-resistant cell lines by microarray analysis, indicating that KIF23 may be involved in the process of paclitaxel resistance in patients with gastric cancer peritoneal metastasis. Therefore, we speculate that the expression of KIF23 may be related to chemotherapy resistance in ovarian cancer. Our results show that overexpression of KIF23 can lead to platinum/paclitaxel or combined drug resistance in patients with ovarian cancer, affecting the overall survival. For PFS, overexpression of KIF23 only leads to platinum chemotherapy resistance, but has no significance in paclitaxel chemotherapy resistance or platinum combined paclitaxel chemotherapy resistance of ovarian cancer patients. Therefore, targeted therapy for KIF23 can be regarded as a promising ovarian cancer treatment strategy.
To further explore the molecular mechanism of KIF23 involved in the occurrence and development of ovarian cancer. The results showed that FLG2 mutations were significantly enriched in patients with low KIF23 expression. TP53 mutations were significantly enriched in both high and low expression groups of KIF23. In KIF23 high expression group, TTN mutation was significantly richer than that in low expression group and the mutations of USH2A, OBSCN and NF1, MUC17, DST were significantly different under different expression conditions. Kunstman JW  found that there was USH2A mutation in anaplastic thyroid carcinoma by whole exon sequencing. The mutant peptides presented by II MHC (major histocompatibility complex) in cancer are important targets for cancer immunotherapy. Some studies have shown that TNN and USH2A can be used as the most common mutant genes with predictive effect on new antigens . OBSCN mutation is closely related to breast cancer and colorectal cancer [42–43]. However, the role of these mutations in ovarian cancer is rarely discussed in existing studies. Based on these findings, we further discussed the KEGG pathway of gene mutation, and we found that the high expression mutant group of KIF23 gene was significantly enriched in Dopaminergic synapse, beta-Alanine metabolism, Glycosaminoglycan degradation and other pathways. Beta-Alanine plays an anti-tumor role by inhibiting the migration of cervical cancer and kidney tumor cells . Glycosaminoglycan is involved in multiple signal cascades required for angiogenesis, invasion and metastasis . Therefore, we suggest that KIF23 can affect the occurrence and development of ovarian cancer by regulating these pathways.
Copy number variation ((CNV)) is closely related to genetic and phenotypic diversity of cancer . By identifying the copy number variation of the whole genome of ovarian cancer, the regions with frequent increase and decrease of copy number have been identified. In addition, high-level amplification of CCNE1, RB1, MYC, ERBB2, PIK3CA, EVI1, AKT2, NOTCH3 and FGFR1 genes can be used as a predictive marker of ovarian cancer [47–49]. However, the copy number of KIF23 in ovarian cancer has not been studied. Therefore, we analyzed the KIF23 copy number, and the results showed that KIF23 gene expression increased significantly with the amplification of sample copy number. Our results showed that the high expression of KIF23 in ovarian cancer is partly caused by copy number amplification. GSEA gene enrichment analysis showed that KIF23 highly expressed genes were significantly enriched in DNA replication and cell cycle gene concentration. The expression of genes related to KIF23 expression is mainly involved in biological behaviors such as regulation of cell cycle phase transition, cell cycle checkpoint, cell cycle G2UniM phase transition, G2UniM transition of mitotic cell cycle, DNA replication and so on.