Abstract
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer globally, causing over 900000 deaths annually. Risk factors include aging, diet, obesity, sedentary lifestyle, tobacco use, genetic predisposition, and inflammatory bowel disease. Despite current treatments, survival rates for advanced CRC remain low, highlighting the need for better therapeutic strategies. AIM: To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14 (KIF14) expression within CRC specimens. Additionally, this study aims to investigate the interaction between nitidine chloride (NC) and KIF14, considering their potential as therapeutic targets. METHODS: The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining. The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference (SMD) for KIF14 mRNA levels. The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves, along with measures of sensitivity, specificity, and likelihood ratios. Additionally, clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC. Survival analysis established the prognostic value of KIF14 in CRC. The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis, and molecular docking was utilized to explore the targeting affinity between NC and KIF14. RESULTS: KIF14 was highly expressed in 208 CRC patients. Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples, with an SMD of 1.92 (95%CI: 1.49-2.35). The area under the curve was 0.94 (95%CI: 0.92-0.96), with a sensitivity of 0.85 (95%CI: 0.78-0.90) and a specificity of 0.90 (95%CI: 0.85-0.93). The positive and negative likelihood ratios were 8.38 (95%CI: 5.39-13.02) and 0.17 (95%CI: 0.11-0.26), respectively. At the single-cell level, significant overexpression of KIF14 was observed in CRC cells (P < 0.001), with 35 CRC cell lines dependent on KIF14 for growth. The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets (P < 0.05). Binding energy calculations indicated that KIF14 is a potential target for NC (binding energy: 10.3 kcal/mol). CONCLUSION: KIF14 promotes the growth of CRC cells and acts as an oncogenic factor, potentially serving as a therapeutic target for NC in the treatment of CRC.